Non-Hodgkin&#39;s lymphoma

Back

Consider –

supportive care

Additional treatment recommended for SOME patients in selected patient group

Patients receiving R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, prednisolone) should be considered for prophylactic granulocyte colony-stimulating factor (G-CSF) to prevent treatment-related neutropenia.[180][181][182]

Antimicrobial prophylaxis should be considered if patients have severe neutropenia (absolute neutrophil count <500 cells/microlitre [<0.5 × 10⁹/L]).[184]

diffuse large B-cell lymphoma; stages I-II (bulky [≥7.5 cm] and low risk [smIPI 0-1]) excluding stage II with extensive mesenteric disease: initial presentation

Back

Consider –

CNS prophylaxis

Additional treatment recommended for SOME patients in selected patient group

Central nervous system (CNS) relapse occurs in approximately 5% of patients with diffuse large B-cell lymphoma (DLBCL) following initial treatment, and is associated with a poor prognosis.[127]

The use of CNS prophylaxis is controversial and it is not routinely recommended. CNS prophylaxis can be considered for patients with high-risk disease, including those with a high-risk score on the CNS-International Prognostic Index (i.e., CNS-IPI 4-6); kidney or adrenal gland involvement; testicular lymphoma; primary cutaneous DLBCL, leg type; or stage IE DLBCL of the breast.[70][121][128][129] See Criteria.

The optimal approach to CNS prophylaxis is unclear. Typically, systemic high-dose methotrexate and/or intrathecal methotrexate and/or intrathecal cytarabine are given during or after treatment.[70][129]

In DLBCL patients receiving CNS prophylaxis, CNS relapse rates are similar regardless of route of administration (intrathecal vs. intravenous) and timing (during vs. after treatment).[130][131]

Folinic acid prophylaxis can minimise toxicity associated with methotrexate (e.g., myelosuppression, gastrointestinal toxicity, hepatotoxicity). All patients receiving high-dose methotrexate should receive folinic acid rescue therapy.[70] Glucarpidase should be used to reduce toxic plasma methotrexate concentration in patients with significant renal dysfunction who are receiving high-dose methotrexate.[70]

See local specialist protocol for dosing guidelines.

Primary options

methotrexate

and/or

cytarabine

1st line – R-CHOP-21 (or alternative chemoimmunotherapy) ± radiotherapy

Back

1st line –

R-CHOP-21 (or alternative chemoimmunotherapy) ± radiotherapy

Initial treatment for stage I-II diffuse large B-cell lymphoma (excluding stage II with extensive mesenteric disease) that is bulky (≥7.5 cm) and low risk (stage-modified International Prognostic Index [smIPI] 0-1) is 3-4 cycles of R-CHOP-21 (rituximab plus cyclophosphamide, doxorubicin, vincristine, prednisolone given on day 1 of a 21-day cycle), followed by interim restaging with PET/CT scan.[70]

Depending on metabolic response (assessed using the Deauville criteria; see Criteria), further cycles of R-CHOP-21 (to a total of 6 cycles) with or without involved-site radiotherapy (ISRT), or repeat biopsy (to guide further treatment) is indicated.[70]

R-CHOP is relatively well tolerated, with the main toxicities being haematological (bone marrow suppression), infection (neutropenia), cardiac (from doxorubicin), alopecia, infusion-related respiratory symptoms (with or without bronchospasm), chills, fever, and hypotension (from rituximab).[186]

See local specialist protocol for dosing guidelines.

Primary options

R-CHOP-21

rituximab

and

cyclophosphamide

and

doxorubicin

and

vincristine

and

prednisolone

Secondary options

R-CEOP

rituximab

and

cyclophosphamide

and

etoposide

and

vincristine

and

prednisolone

R-GCVP

rituximab

and

gemcitabine

and

cyclophosphamide

and

vincristine

and

prednisolone

R-mini-CHOP

rituximab

and

cyclophosphamide

and

doxorubicin

and

vincristine

and

prednisolone

Back

Consider –

supportive care

Additional treatment recommended for SOME patients in selected patient group

Antimicrobial prophylaxis should be considered if patients have severe neutropenia (absolute neutrophil count <500 cells/microlitre [<0.5 × 10⁹/L]).[184]

diffuse large B-cell lymphoma; stages I-II (non-bulky or bulky, and high risk [smIPI >1]) excluding stage II with extensive mesenteric disease: initial presentation

Back

Consider –

CNS prophylaxis

Additional treatment recommended for SOME patients in selected patient group

Central nervous system (CNS) relapse occurs in approximately 5% of patients with diffuse large B-cell lymphoma (DLBCL) following initial treatment, and is associated with a poor prognosis.[127]

In DLBCL patients receiving CNS prophylaxis, CNS relapse rates are similar regardless of route of administration (intrathecal vs. intravenous) and timing (during vs. after treatment).[130][131]

See local specialist protocol for dosing guidelines.

Primary options

methotrexate

and/or

cytarabine

1st line – R-CHOP-21 or Pola-R-CHP (or alternative chemoimmunotherapy)

Back

1st line –

R-CHOP-21 or Pola-R-CHP (or alternative chemoimmunotherapy)

Initial treatment for stage I-II diffuse large B-cell lymphoma (excluding stage II with extensive mesenteric disease) that is non-bulky or bulky, and high risk (stage-modified International Prognostic Index [smIPI] >1) is R-CHOP-21 (rituximab plus cyclophosphamide, doxorubicin, vincristine, prednisolone given on day 1 of a 21-day cycle) or Pola-R-CHP (polatuzumab vedotin plus rituximab, cyclophosphamide, doxorubicin, and prednisolone) for 2-4 cycles, followed by interim restaging with PET/CT or CT scan.[70]

Depending on metabolic response (assessed using the Deauville criteria; see Criteria), further cycles of the initial regimen (to a total of 6 cycles), or repeat biopsy (to guide further treatment) is indicated.[70]

See local specialist protocol for dosing guidelines.

Primary options

R-CHOP-21

rituximab

and

cyclophosphamide

and

doxorubicin

and

vincristine

and

prednisolone

Pola-R-CHP

polatuzumab vedotin

and

rituximab

and

cyclophosphamide

and

doxorubicin

and

prednisolone

Secondary options

R-CEOP

rituximab

and

cyclophosphamide

and

etoposide

and

vincristine

and

prednisolone

R-GCVP

rituximab

and

gemcitabine

and

cyclophosphamide

and

vincristine

and

prednisolone

R-mini-CHOP

rituximab

and

cyclophosphamide

and

doxorubicin

and

vincristine

and

prednisolone

Back

Consider –

supportive care

Additional treatment recommended for SOME patients in selected patient group

Antimicrobial prophylaxis should be considered if patients have severe neutropenia (absolute neutrophil count <500 cells/microlitre [<0.5 × 10⁹/L]).[184]

diffuse large B-cell lymphoma; stage II with extensive mesenteric disease; stages III-IV: initial presentation

Back

Consider –

CNS prophylaxis

Additional treatment recommended for SOME patients in selected patient group

Central nervous system (CNS) relapse occurs in approximately 5% of patients with diffuse large B-cell lymphoma (DLBCL) following initial treatment, and is associated with a poor prognosis.[127]

In DLBCL patients receiving CNS prophylaxis, CNS relapse rates are similar regardless of route of administration (intrathecal vs. intravenous) and timing (during vs. after treatment).[130][131]

See local specialist protocol for dosing guidelines.

Primary options

methotrexate

and/or

cytarabine

1st line – R-CHOP-21 or Pola-R-CHP or R-EPOCH (or alternative chemoimmunotherapy)

Back

1st line –

R-CHOP-21 or Pola-R-CHP or R-EPOCH (or alternative chemoimmunotherapy)

Initial treatment for diffuse large B-cell lymphoma that is stage II with extensive mesenteric disease, or stages III-IV, is R-CHOP-21 (rituximab plus cyclophosphamide, doxorubicin, vincristine, prednisolone given on day 1 of a 21-day cycle) or Pola-R-CHP (polatuzumab vedotin plus rituximab, cyclophosphamide, doxorubicin, and prednisolone; for patients with International Prognostic Index [IPI] ≥2) for 2-4 cycles, followed by interim restaging with PET/CT or CT scan.[70]

Other recommended treatment regimens include dose-adjusted R-EPOCH (rituximab plus etoposide, prednisolone, vincristine, cyclophosphamide, and doxorubicin).[70] Dose-adjusted R-EPOCH should be considered for patients with a poor prognosis (e.g., those with MYC translocations and BCL2 and/or BCL6 rearrangements [i.e., 'double-hit' or 'triple-hit']) or those with HIV infection.[70][126]

See local specialist protocol for dosing guidelines.

Primary options

R-CHOP-21

rituximab

and

cyclophosphamide

and

doxorubicin

and

vincristine

and

prednisolone

Pola-R-CHP

polatuzumab vedotin

and

rituximab

and

cyclophosphamide

and

doxorubicin

and

prednisolone

Secondary options

R-EPOCH

rituximab

and

etoposide

and

prednisolone

and

vincristine

and

cyclophosphamide

and

doxorubicin

R-CEOP

rituximab

and

cyclophosphamide

and

etoposide

and

vincristine

and

prednisolone

R-GCVP

rituximab

and

gemcitabine

and

cyclophosphamide

and

vincristine

and

prednisolone

R-mini-CHOP

rituximab

and

cyclophosphamide

and

doxorubicin

and

vincristine

and

prednisolone

Back

Consider –

supportive care

Additional treatment recommended for SOME patients in selected patient group

Antimicrobial prophylaxis should be considered if patients have severe neutropenia (absolute neutrophil count <500 cells/microlitre [<0.5 × 10⁹/L]).[184]

diffuse large B-cell lymphoma; primary refractory disease or early relapse (<12 months)

Back

Consider –

CNS prophylaxis

Additional treatment recommended for SOME patients in selected patient group

Central nervous system (CNS) relapse occurs in approximately 5% of patients with diffuse large B-cell lymphoma (DLBCL) following initial treatment, and is associated with a poor prognosis.[127]

In DLBCL patients receiving CNS prophylaxis, CNS relapse rates are similar regardless of route of administration (intrathecal vs. intravenous) and timing (during vs. after treatment).[130][131]

See local specialist protocol for dosing guidelines.

Primary options

methotrexate

and/or

cytarabine

1st line – chimeric antigen receptor (CAR) T-cell therapy, or bispecific antibody therapy, or monoclonal antibody therapy, or salvage chemotherapy/chemoimmunotherapy, or palliative radiotherapy

Back

1st line –

chimeric antigen receptor (CAR) T-cell therapy, or bispecific antibody therapy, or monoclonal antibody therapy, or salvage chemotherapy/chemoimmunotherapy, or palliative radiotherapy

Approximately 40% of patients with diffuse large B-cell lymphoma will have refractory or relapsed disease, most of whom will ultimately die from their lymphoma.[132][133]

Refractory and relapsed disease should be confirmed by repeat biopsy before proceeding with salvage treatment.[70][134]

CAR T-cell therapy is recommended for patients who have primary refractory disease or early relapse (<12 months).[70] Options include axicabtagene ciloleucel or lisocabtagene maraleucel.

Patients should receive bridging therapy (e.g., with chemotherapy) as clinically indicated, while waiting for administration of CAR T-cell therapy.[70]

Patients should be carefully assessed for suitability for CAR T-cell therapy. Toxicities include cytokine release syndrome, neurotoxicity, secondary malignancies (e.g., T-cell malignancies), and cardiovascular complications, which may limit use of CAR T-cell therapy.[135][136][137][138][139]

Patients with primary refractory disease or early relapse (<12 months) who are unsuitable for CAR T-cell therapy can be considered for a clinical trial or an alternative salvage regimen, including (if not previously given): epcoritamab plus GemOx (gemcitabine plus oxaliplatin); glofitamab plus GemOx; polatuzumab vedotin with or without bendamustine plus rituximab; polatuzumab vedotin plus mosunetuzumab; tafasitamab plus lenalidomide (excluding primary refractory disease); or salvage chemotherapy (e.g., DHA [dexamethasone plus cytarabine] plus a platinum agent [cisplatin, carboplatin, or oxaliplatin]; gemcitabine plus dexamethasone and a platinum agent [cisplatin or carboplatin]; ICE [ifosfamide, carboplatin, etoposide]) with or without rituximab.[70]

Palliative involved-site radiotherapy (ISRT) or best supportive care is also an option for patients with primary refractory disease or early relapse who are unsuitable for CAR T-cell therapy.[70]

See local specialist protocol for dosing guidelines.

Primary options

axicabtagene ciloleucel

lisocabtagene maraleucel

Secondary options

epcoritamab

and

gemcitabine

and

oxaliplatin

glofitamab

and

gemcitabine

and

oxaliplatin

polatuzumab vedotin

and

bendamustine

and

rituximab

polatuzumab vedotin

and

mosunetuzumab

tafasitamab

and

lenalidomide

DHA + platinum agent

dexamethasone

-- AND --

cytarabine

-- AND --

cisplatin

carboplatin

oxaliplatin

DHA + platinum agent + rituximab

dexamethasone

-- AND --

cytarabine

-- AND --

cisplatin

carboplatin

oxaliplatin

-- AND --

rituximab

gemcitabine

-- AND --

dexamethasone

-- AND --

cisplatin

carboplatin

gemcitabine

-- AND --

dexamethasone

-- AND --

cisplatin

carboplatin

-- AND --

rituximab

ICE

ifosfamide

and

carboplatin

and

etoposide

ICE + rituximab

ifosfamide

and

carboplatin

and

etoposide

and

rituximab

2nd line – chimeric antigen receptor (CAR) T-cell therapy, or bispecific antibody therapy, or brentuximab vedotin + lenalidomide + rituximab, or loncastuximab tesirine, or selinexor, or palliative radiotherapy

Back

Consider –

supportive care

Additional treatment recommended for SOME patients in selected patient group

Antimicrobial prophylaxis should be considered if patients have severe neutropenia (absolute neutrophil count <500 cells/microlitre [<0.5 × 10⁹/L]).[184]

Patients on high-dose ifosfamide should receive mesna to prevent haemorrhagic cystitis.[185]

All patients receiving salvage chemotherapy should receive a granulocyte colony-stimulating factor (G-CSF) concomitantly to prevent treatment-related neutropenia.[181][183]

Back

2nd line –

chimeric antigen receptor (CAR) T-cell therapy, or bispecific antibody therapy, or brentuximab vedotin + lenalidomide + rituximab, or loncastuximab tesirine, or selinexor, or palliative radiotherapy

For adults with relapsed or refractory diffuse large B-cell lymphoma after two or more lines of systemic therapy, subsequent treatment options include (if not used previously): CAR T-cell therapy (axicabtagene ciloleucel; tisagenlecleucel; lisocabtagene maraleucel); bispecific antibody therapy (epcoritamab, glofitamab); brentuximab vedotin plus lenalidomide plus rituximab (for CD30-positive disease); loncastuximab tesirine; selinexor (including patients with disease progression after CAR T-cell therapy).[70]

Palliative involved-site radiotherapy (ISRT) or best supportive care is also an option if patients are unsuitable for subsequent treatment following two or more lines of systemic therapy.[70]

See local specialist protocol for dosing guidelines.

Primary options

axicabtagene ciloleucel

tisagenlecleucel

lisocabtagene maraleucel

epcoritamab

glofitamab

brentuximab vedotin

and

lenalidomide

and

rituximab

loncastuximab tesirine

selinexor

diffuse large B-cell lymphoma; late relapse (>12 months): intention to proceed to autologous stem cell transplant

Back

Consider –

supportive care

Additional treatment recommended for SOME patients in selected patient group

Antimicrobial prophylaxis should be considered if patients have severe neutropenia (absolute neutrophil count <500 cells/microlitre [<0.5 × 10⁹/L]).[184]

1st line – salvage chemotherapy/chemoimmunotherapy

Back

1st line –

salvage chemotherapy/chemoimmunotherapy

Salvage chemotherapy regimens are recommended for patients with diffuse large B-cell lymphoma with late relapse (>12 months) who are eligible for intensive consolidation and intended for autologous stem cell transplant (based on age, general fitness, comorbidities).[70]

Preferred salvage chemotherapy regimens include: dexamethasone and cytarabine (DHA) and a platinum agent (cisplatin, carboplatin, or oxaliplatin) with or without rituximab; gemcitabine plus dexamethasone and a platinum agent (cisplatin or carboplatin) with or without rituximab; ifosfamide, carboplatin, and etoposide (ICE) with or without rituximab.[70]

See local specialist protocol for dosing guidelines.

Primary options

DHA + platinum agent

dexamethasone

-- AND --

cytarabine

-- AND --

cisplatin

carboplatin

oxaliplatin

DHA + platinum agent + rituximab

dexamethasone

-- AND --

cytarabine

-- AND --

cisplatin

carboplatin

oxaliplatin

-- AND --

rituximab

gemcitabine

-- AND --

dexamethasone

-- AND --

cisplatin

carboplatin

gemcitabine

-- AND --

dexamethasone

-- AND --

cisplatin

carboplatin

-- AND --

rituximab

ICE

ifosfamide

and

carboplatin

and

etoposide

ICE + rituximab

ifosfamide

and

carboplatin

and

etoposide

and

rituximab

Consider – autologous stem cell transplant ± radiotherapy, or allogeneic stem cell transplant ± radiotherapy, or chimeric antigen receptor (CAR) T-cell therapy

Back

Consider –

autologous stem cell transplant ± radiotherapy, or allogeneic stem cell transplant ± radiotherapy, or chimeric antigen receptor (CAR) T-cell therapy

Additional treatment recommended for SOME patients in selected patient group

If a complete or partial response is achieved following salvage chemotherapy, then consolidation (high-dose) therapy with autologous stem cell transplant (with or without involved-site radiotherapy [ISRT]) is recommended for suitable candidates (e.g., based on age, general fitness, comorbidities).[70]

Allogeneic stem cell transplant (with or without ISRT) may be considered for consolidation therapy in select patients (e.g., those with stem cell mobilisation failure and persistent bone marrow involvement) if a donor is available.[70]

CAR T-cell therapy (axicabtagene ciloleucel; tisagenlecleucel; lisocabtagene maraleucel) is an option if a partial response is achieved following salvage chemotherapy.[70]

See local specialist protocol for dosing guidelines.

Primary options

axicabtagene ciloleucel

tisagenlecleucel

lisocabtagene maraleucel

Back

Consider –

supportive care

Additional treatment recommended for SOME patients in selected patient group

Antimicrobial prophylaxis should be considered if patients have severe neutropenia (absolute neutrophil count <500 cells/microlitre [<0.5 × 10⁹/L]).[184]

Patients on high-dose ifosfamide should receive mesna to prevent haemorrhagic cystitis.[185]

All patients receiving salvage chemotherapy should receive a granulocyte colony-stimulating factor (G-CSF) concomitantly to prevent treatment-related neutropenia.[181][183]

Back

2nd line –

chimeric antigen receptor (CAR) T-cell therapy, or bispecific antibody therapy, or brentuximab vedotin + lenalidomide + rituximab, or loncastuximab tesirine, or selinexor, or palliative radiotherapy

Palliative involved-site radiotherapy (ISRT) or best supportive care is also an option if patients are unsuitable for subsequent treatment following two or more lines of systemic therapy.[70]

See local specialist protocol for dosing guidelines.

Primary options

axicabtagene ciloleucel

tisagenlecleucel

lisocabtagene maraleucel

epcoritamab

glofitamab

brentuximab vedotin

and

lenalidomide

and

rituximab

loncastuximab tesirine

selinexor

diffuse large B-cell lymphoma; late relapse (>12 months): no intention to proceed to autologous stem cell transplant

Back

Consider –

supportive care

Additional treatment recommended for SOME patients in selected patient group

Antimicrobial prophylaxis should be considered if patients have severe neutropenia (absolute neutrophil count <500 cells/microlitre [<0.5 × 10⁹/L]).[184]

Back

1st line –

chimeric antigen receptor (CAR) T-cell therapy, or bispecific antibody therapy, or monoclonal antibody therapy, or salvage chemotherapy/chemoimmunotherapy, or palliative radiotherapy

For patients with late relapse (>12 months) who are not intended for autologous stem cell transplant (ASCT), salvage therapy includes (if not previously given): CAR T-cell therapy (lisocabtagene maraleucel, with bridging therapy as needed); epcoritamab plus GemOx (gemcitabine plus oxaliplatin); glofitamab plus GemOx; polatuzumab vedotin with or without bendamustine plus rituximab; polatuzumab vedotin plus mosunetuzumab; tafasitamab plus lenalidomide; or second-line chemotherapy (e.g., CEOP [cyclophosphamide, etoposide, vincristine, prednisolone]) with or without rituximab.[70]

Palliative involved-site radiotherapy (ISRT) or best supportive care is also an option for patients with late relapse who are not intended for ASCT.[70]

See local specialist protocol for dosing guidelines.

Primary options

lisocabtagene maraleucel

epcoritamab

and

gemcitabine

and

oxaliplatin

glofitamab

and

gemcitabine

and

oxaliplatin

polatuzumab vedotin

and

bendamustine

and

rituximab

polatuzumab vedotin

and

mosunetuzumab

tafasitamab

and

lenalidomide

CEOP

cyclophosphamide

and

etoposide

and

vincristine

and

prednisolone

CEOP + rituximab

cyclophosphamide

and

etoposide

and

vincristine

and

prednisolone

and

rituximab

Back

Consider –

supportive care

Additional treatment recommended for SOME patients in selected patient group

Antimicrobial prophylaxis should be considered if patients have severe neutropenia (absolute neutrophil count <500 cells/microlitre [<0.5 × 10⁹/L]).[184]

Patients on high-dose cyclophosphamide should receive mesna to prevent haemorrhagic cystitis.[185]

All patients receiving salvage chemotherapy should receive a granulocyte colony-stimulating factor (G-CSF) concomitantly to prevent treatment-related neutropenia.[181][183]

Back

2nd line –

chimeric antigen receptor (CAR) T-cell therapy, or bispecific antibody therapy, or brentuximab vedotin + lenalidomide + rituximab, or loncastuximab tesirine, or selinexor, or palliative radiotherapy

For adults with relapsed or refractory diffuse large B-cell lymphoma after two or more lines of systemic therapy, subsequent treatment options include (if not used previously): CAR T-cell therapy (axicabtagene ciloleucel; tisagenlecleucel; lisocabtagene maraleucel); bispecific antibody therapy (epcoritamab, glofitamab); brentuximab vedotin plus lenalidomide and rituximab (for CD30-positive disease); loncastuximab tesirine; selinexor (including patients with disease progression after CAR T-cell therapy).[70]

Palliative involved-site radiotherapy (ISRT) or best supportive care is also an option if patients are unsuitable for subsequent treatment following two or more lines of systemic therapy.[70]

See local specialist protocol for dosing guidelines.

Primary options

axicabtagene ciloleucel

tisagenlecleucel

lisocabtagene maraleucel

epcoritamab

glofitamab

brentuximab vedotin

and

lenalidomide

and

rituximab

loncastuximab tesirine

selinexor

primary mediastinal large B-cell lymphoma: initial presentation

Back

Consider –

supportive care

Additional treatment recommended for SOME patients in selected patient group

Antimicrobial prophylaxis should be considered if patients have severe neutropenia (absolute neutrophil count <500 cells/microlitre [<0.5 × 10⁹/L]).[184]

1st line – chemotherapy ± radiotherapy

Back

1st line –

chemotherapy ± radiotherapy

First-line treatment options for primary mediastinal large B-cell lymphoma (PMBCL) include: dose-adjusted R-EPOCH (rituximab plus etoposide, prednisolone, vincristine, cyclophosphamide, and doxorubicin) for 6 cycles; R-CHOP-21 (rituximab plus cyclophosphamide, doxorubicin, vincristine, prednisolone given on day 1 of a 21-day cycle) for 6 cycles ± involved-site radiotherapy (ISRT) to the mediastinum; or R-CHOP-14 (rituximab plus cyclophosphamide, doxorubicin, vincristine, prednisolone given on day 1 of a 14-day cycle) for 4-6 cycles.[70]

Intensive regimens (e.g., dose-adjusted R-EPOCH or R-CHOP-14) are usually preferred in fit patients, and in younger patients (as it avoids the need for radiotherapy which is associated with long-term complications).[70][140]

Patients treated with 4 cycles of R-CHOP-14 who achieve a complete response can receive consolidation therapy with 3 cycles of ICE (ifosfamide, carboplatin, and etoposide), with or without rituximab.[70][141]

See local specialist protocol for dosing guidelines.

Primary options

R-EPOCH

rituximab

and

etoposide

and

prednisolone

and

vincristine

and

cyclophosphamide

and

doxorubicin

R-CHOP-21

rituximab

and

cyclophosphamide

and

doxorubicin

and

vincristine

and

prednisolone

Secondary options

ICE

ifosfamide

and

carboplatin

and

etoposide

ICE + rituximab

ifosfamide

and

carboplatin

and

etoposide

and

rituximab

primary mediastinal large B-cell lymphoma; partial response to initial treatment, or progressive/relapsed/refractory disease

Back

Consider –

supportive care

Additional treatment recommended for SOME patients in selected patient group

Patients on high-dose cyclophosphamide or ifosfamide should receive mesna to prevent haemorrhagic cystitis.[185]

Mesna is not required for less intensive cyclophosphamide-containing regimens (e.g., R-CHOP-21 [rituximab plus cyclophosphamide, doxorubicin, vincristine, prednisolone given on day 1 of a 21-day cycle]).

Patients receiving R-CHOP should be considered for prophylactic granulocyte colony-stimulating factor (G-CSF) to prevent treatment-related neutropenia.[180][181][182]

Antimicrobial prophylaxis should be considered if patients have severe neutropenia (absolute neutrophil count <500 cells/microlitre [<0.5 × 10⁹/L]).[184]

1st line – radiotherapy, or pembrolizumab, or nivolumab ± brentuximab vedotin

Back

1st line –

radiotherapy, or pembrolizumab, or nivolumab ± brentuximab vedotin

Patients with primary mediastinal large B-cell lymphoma (PMBCL) who achieve a partial response with initial treatment, or who have progressive, relapsed, or refractory disease (confirmed by biopsy), can be considered for second-line treatment, which includes: involved-site radiotherapy (if a partial response is achieved and confirmed by biopsy); pembrolizumab; or nivolumab with or without brentuximab vedotin.[70]

Treatment options for relapsed or refractory diffuse large B-cell lymphoma (DLBCL) can also be considered in these patients.

See local specialist protocol for dosing guidelines.

Primary options

pembrolizumab

nivolumab

and

brentuximab vedotin

primary CNS lymphoma: initial presentation

Back

Consider –

supportive care

Additional treatment recommended for SOME patients in selected patient group

Antimicrobial prophylaxis should be considered if patients have severe neutropenia (absolute neutrophil count <500 cells/microlitre [<0.5 × 10⁹/L]).[184]

1st line – methotrexate-based therapy ± radiotherapy ± consolidation therapy

Back

1st line –

methotrexate-based therapy ± radiotherapy ± consolidation therapy

Optimal treatment for primary CNS lymphoma (PCNSL) involves two phases: induction and consolidation.

All patients who are clinically fit should be treated with high-dose methotrexate-based induction therapy.[79]

Induction therapy regimens include: high-dose methotrexate plus rituximab (with or without temozolomide); high-dose methotrexate plus vincristine, procarbazine, and rituximab (R-MPV); and high-dose methotrexate plus cytarabine, thiotepa, and rituximab.[79][143]

Whole-brain radiotherapy (WBRT) may be used with palliative intent in patients who are not candidates for systemic therapy.[79] While PCNSL is sensitive to WBRT, response is usually transient and neurotoxicity may occur (particularly in older patients).[143]

Patients with ocular involvement may be considered for ocular radiotherapy (if unresponsive to systemic therapy) or referred to a specialist ophthalmologist for intraocular methotrexate therapy.[79]

Patients achieving a complete response to induction therapy can be considered for consolidation therapy. Options include: high-dose chemotherapy (e.g., cytarabine plus thiotepa followed by carmustine plus thiotepa; or thiotepa plus busulfan and cyclophosphamide) with autologous stem cell rescue; or high-dose cytarabine with or without etoposide.[79][143][144][145][146]

Low-dose WBRT may be considered for consolidation if systemic consolidation therapy is not an option.[147]

See local specialist protocol for dosing guidelines.

Primary options

methotrexate

and

rituximab

methotrexate

and

rituximab

and

temozolomide

R-MPV

methotrexate

and

vincristine

and

procarbazine

and

rituximab

methotrexate

and

cytarabine

and

thiotepa

and

rituximab

Secondary options

thiotepa

and

cytarabine

and

carmustine

thiotepa

and

busulfan

and

cyclophosphamide

cytarabine

and

etoposide

Back

Plus –

supportive care

Treatment recommended for ALL patients in selected patient group

Antimicrobial prophylaxis should be considered if patients have severe neutropenia (absolute neutrophil count <500 cells/microlitre [<0.5 × 10⁹/L]).[184]

Patients on high-dose cyclophosphamide should receive mesna to prevent haemorrhagic cystitis.[185]

primary CNS lymphoma: with residual disease after induction therapy

Back

Consider –

antiretroviral therapy (ART)

Additional treatment recommended for SOME patients in selected patient group

Primary CNS lymphoma is commonly associated with HIV infection.[65]

If the patient is living with HIV, ART should be administered concurrently with systemic therapy.[79]

ART consists of multiple drugs from several classes and varies significantly depending on each individual patient with HIV. Request infectious disease consult to determine appropriate regimen for each patient.

For detailed information on ART, see HIV in adults.

1st line – high-dose cytarabine ± etoposide, or temozolomide, or whole-brain radiotherapy

Back

1st line –

high-dose cytarabine ± etoposide, or temozolomide, or whole-brain radiotherapy

Patients with primary CNS lymphoma who have residual disease after induction therapy can be consider for treatment with: high-dose cytarabine with or without etoposide; or temozolomide (after whole-brain radiotherapy [WBRT]); or WBRT; or best supportive care.[79]

See local specialist protocol for dosing guidelines.

Primary options

cytarabine

and

etoposide

temozolomide

Back

Plus –

supportive care

Treatment recommended for ALL patients in selected patient group

Antimicrobial prophylaxis should be considered if patients have severe neutropenia (absolute neutrophil count <500 cells/microlitre [<0.5 × 10⁹/L]).[184]

primary CNS lymphoma: relapsed or refractory disease

Back

Consider –

antiretroviral therapy (ART)

Additional treatment recommended for SOME patients in selected patient group

Primary CNS lymphoma is commonly associated with HIV infection.[65]

If the patient is living with HIV, ART should be administered concurrently with systemic therapy.[79]

For detailed information on ART, see HIV in adults.

1st line – chemotherapy, or methotrexate-based therapy, or targeted therapy

Back

1st line –

chemotherapy, or methotrexate-based therapy, or targeted therapy

Optimal treatment for relapsed or refractory primary CNS lymphoma is unclear.

Treatment is typically based on prior treatments received and time to relapse (i.e., early [<12 months] vs. late [≥12 months]).[79]

Systemic therapy options include an alternative chemotherapy regimen if relapse is early, or retreatment with high-dose methotrexate-based therapy if relapse is late.[79]

Targeted therapies can also be considered for relapsed or refractory primary CNS lymphoma, including ibrutinib (a covalent Bruton's tyrosine kinase [BTK] inhibitor), lenalidomide, or pomalidomide.[79]

Enrollment in a clinical trial should be encouraged.

Back

Plus –

supportive care

Treatment recommended for ALL patients in selected patient group

Antimicrobial prophylaxis should be considered if patients have severe neutropenia (absolute neutrophil count <500 cells/microlitre [<0.5 × 10⁹/L]).[184]

primary effusion lymphoma

Back

Consider –

antiretroviral therapy (ART)

Additional treatment recommended for SOME patients in selected patient group

Primary CNS lymphoma is commonly associated with HIV infection.[65]

If the patient is living with HIV, ART should be administered concurrently with systemic therapy.[79]

For detailed information on ART, see HIV in adults.

1st line – EPOCH or CHOP

Back

1st line –

EPOCH or CHOP

The optimal management of primary effusion lymphoma (PEL) is unclear.

Treatment options include EPOCH (etoposide, prednisolone, vincristine, cyclophosphamide, and doxorubicin) or CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone).[70]

CHOP is relatively well tolerated, with the main toxicities being haematological (bone marrow suppression), infection (neutropenia), cardiac (from doxorubicin), and alopecia.[186]

Rituximab is not indicated because most cases of PEL are CD20-negative.

See local specialist protocol for dosing guidelines.

Primary options

EPOCH

etoposide

and

prednisolone

and

vincristine

and

cyclophosphamide

and

doxorubicin

CHOP

cyclophosphamide

and

doxorubicin

and

vincristine

and

prednisolone

Back

Consider –

antiretroviral therapy (ART)

Additional treatment recommended for SOME patients in selected patient group

Primary effusion lymphoma (PEL) occurs most commonly in immunocompromised patients (e.g., those living with HIV).[1]

ART is important (along with chemotherapy) in treating patients with HIV-positive PEL.[192]

For detailed information on ART, see HIV in adults.

Burkitt's lymphoma: initial presentation

Back

Consider –

supportive care

Additional treatment recommended for SOME patients in selected patient group

Antimicrobial prophylaxis should be considered if patients have severe neutropenia (absolute neutrophil count <500 cells/microlitre [<0.5 × 10⁹/L]).[184]

Patients on high-dose cyclophosphamide should receive mesna to prevent haemorrhagic cystitis.[185]

Mesna is not required for less intensive cyclophosphamide-containing regimens (e.g., CHOP [cyclophosphamide, doxorubicin, vincristine, prednisolone]).

1st line – R-CODOX-M, or R-CODOX-M/R-IVAC, or R-EPOCH ± intrathecal methotrexate, or R-hyper-CVAD

Back

1st line –

R-CODOX-M, or R-CODOX-M/R-IVAC, or R-EPOCH ± intrathecal methotrexate, or R-hyper-CVAD

Burkitt's lymphoma is a highly aggressive NHL that requires treatment with intensive multiagent chemotherapy regimens.[70] CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone) is not an adequate regimen.

Treatment is based on age and risk-stratification (i.e., low risk or high risk).[70] Patients with normal serum lactate dehydrogenase (LDH) and stage I disease (single extra-abdominal mass <10 cm) or a completely resected abdominal lesion are considered low risk.[70]

Patients with stage I disease and an abdominal mass or extra-abdominal mass >10 cm, or with stage II to IV disease, are considered high risk.[70]

Initial treatment for patients aged <60 years with low-risk disease includes: R-CODOX-M (rituximab plus cyclophosphamide, doxorubicin, and vincristine with intrathecal methotrexate and cytarabine followed by high-dose systemic methotrexate); dose-adjusted R-EPOCH (rituximab plus etoposide, prednisolone, vincristine, cyclophosphamide, and doxorubicin) for 2 cycles followed by interim PET/CT scan (depending on metabolic response, additional cycles of dose-adjusted R-EPOCH with or without intrathecal methotrexate are indicated); R-hyper-CVAD (rituximab plus cyclophosphamide, vincristine, doxorubicin, and dexamethasone, alternating with methotrexate and cytarabine).[70]

Initial treatment for patients aged <60 years with high-risk disease includes: R-CODOX-M alternating with R-IVAC (rituximab plus ifosfamide, cytarabine, etoposide, and intrathecal methotrexate); R-hyper-CVAD; dose-adjusted R-EPOCH plus intrathecal methotrexate (for those not able to tolerate aggressive regimens).[70]

Initial treatment for patients aged ≥60 years with low-risk disease is dose-adjusted R-EPOCH for 2 cycles followed by interim PET/CT scan (depending on metabolic response, additional cycles of dose-adjusted R-EPOCH with or without intrathecal methotrexate are indicated).[70]

Initial treatment for patients aged ≥60 years with high-risk disease is dose-adjusted R-EPOCH plus intrathecal methotrexate (for those presenting with symptomatic CNS disease).[70]

Adequate CNS prophylaxis/therapy with high-dose systemic methotrexate and intrathecal methotrexate and/or cytarabine is recommended with all regimens for Burkitt's lymphoma due to the high risk for CNS involvement.[70]

A clinical trial (if available) or palliative involved-site radiotherapy (ISRT) is recommended for patients who do not achieve a complete response after initial treatment.[70]

See local specialist protocol for dosing guidelines.

Primary options

R-CODOX-M

rituximab

and

cyclophosphamide

and

doxorubicin

and

vincristine

and

methotrexate

and

cytarabine

R-IVAC

rituximab

and

ifosfamide

and

cytarabine

and

etoposide

and

methotrexate

R-EPOCH

rituximab

and

etoposide

and

prednisolone

and

vincristine

and

cyclophosphamide

and

doxorubicin

R-EPOCH + intrathecal methotrexate

rituximab

and

etoposide

and

prednisolone

and

vincristine

and

cyclophosphamide

and

doxorubicin

and

methotrexate

R-hyper-CVAD

rituximab

and

cyclophosphamide

and

vincristine

and

doxorubicin

and

dexamethasone

and

methotrexate

and

cytarabine

Burkitt's lymphoma: relapsed or refractory disease

Back

Plus –

supportive care

Treatment recommended for ALL patients in selected patient group

Tumour lysis syndrome (TLS) is an oncological emergency, particularly among patients with Burkitt's lymphoma. Vigorous hydration (with intravenous fluids), phosphate-binding agents, and hypouricaemic agents (e.g., allopurinol or rasburicase) should be used to prevent or treat TLS. TLS is characterised by hyperkalaemia, hyperphosphataemia, hyperuricaemia, and hypocalcaemia, which can occur following treatment for NHL (or spontaneously in rare cases).

Patients on high-dose cyclophosphamide or ifosfamide should receive mesna to prevent haemorrhagic cystitis.[185]

Antimicrobial prophylaxis should be considered if patients have severe neutropenia (absolute neutrophil count <500 cells/microlitre [<0.5 × 10⁹/L].[184]

1st line – salvage chemotherapy ± consolidation therapy

Back

1st line –

salvage chemotherapy ± consolidation therapy

Optimal treatment for relapsed or refractory Burkitt's lymphoma is unclear. Patients should be treated in a clinical trial where available.

If relapse occurs >6-18 months after initial treatment and beyond, the following regimens can be considered for second-line treatment (if not previously used): dose-adjusted R-EPOCH (rituximab plus etoposide, prednisolone, vincristine, cyclophosphamide, and doxorubicin) plus intrathecal methotrexate; R-ICE (rituximab plus ifosfamide, carboplatin, and etoposide) plus intrathecal methotrexate (if not received previously); R-IVAC (rituximab plus ifosfamide, cytarabine, and etoposide) plus intrathecal methotrexate (if not received previously).[70]

Consolidation therapy with autologous stem cell transplant (with or without involved-site radiotherapy [ISRT]) should be considered after second-line treatment, depending on response.[70] Allogeneic stem cell transplant (with or without ISRT) may be considered for consolidation therapy in select patients (e.g., those with stem cell mobilisation failure and persistent bone marrow involvement) if a donor is available.

Patients with relapse occurring <6 months after initial therapy, or who do not respond to second-line treatment or have progressive disease, should be considered for a clinical trial or best supportive care (including palliative ISRT).[70]

See local specialist protocol for dosing guidelines.

Primary options

R-EPOCH + intrathecal methotrexate

rituximab

and

etoposide

and

prednisolone

and

vincristine

and

cyclophosphamide

and

doxorubicin

and

methotrexate

R-ICE

rituximab

and

ifosfamide

and

carboplatin

and

etoposide

R-ICE + intrathecal methotrexate

rituximab

and

ifosfamide

and

carboplatin

and

etoposide

and

methotrexate

R-IVAC

rituximab

and

ifosfamide

and

etoposide

and

cytarabine

R-IVAC + intrathecal methotrexate

rituximab

and

ifosfamide

and

etoposide

and

cytarabine

and

methotrexate

mantle cell lymphoma without TP53 mutation; localised disease: initial presentation

Back

Plus –

supportive care

Treatment recommended for ALL patients in selected patient group

Patients on high-dose cyclophosphamide or ifosfamide should receive mesna to prevent haemorrhagic cystitis.[185]

Antimicrobial prophylaxis should be considered if patients have severe neutropenia (absolute neutrophil count <500 cells/microlitre [<0.5 × 10⁹/L]).[184]

1st line – induction therapy (less aggressive) ± radiotherapy, or radiotherapy alone, or active surveillance

Back

1st line –

induction therapy (less aggressive) ± radiotherapy, or radiotherapy alone, or active surveillance

Treatment for mantle cell lymphoma (MCL) should be individualised based on disease stage, disease characteristics (e.g., TP53 mutation status), symptoms, and patient factors (e.g., age, performance status, comorbidities, desire/eligibility for aggressive therapy).[70][134][148]

A small proportion of patients with MCL (10% to 15%) have indolent disease and can undergo active surveillance if asymptomatic.[70][132] Typical characteristics of indolent MCL include: IGHV-mutated; SOX11-negative; leukaemic or non-nodal MCL with splenomegaly; gastrointestinal, blood, or bone marrow involvement; low tumour burden; and Ki-67 proliferation fraction <10%.[70]

Most patients with MCL have rapidly progressing advanced-stage disease and need treatment at the time of diagnosis.[70][132]

Patients should be enroled in a clinical trial if possible.[70]

Initial treatment is typically given in phases (induction, consolidation, maintenance).

Less aggressive induction therapy is recommended for patients with localised disease (stage I or stage II [non-bulky]) without TP53 mutations.[70] Options include: acalabrutinib (a Bruton's tyrosine kinase [BTK] inhibitor) plus bendamustine plus rituximab; bendamustine plus rituximab; VR-CAP (bortezomib, rituximab, cyclophosphamide, doxorubicin, and prednisolone); R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone); lenalidomide plus rituximab; acalabrutinib plus rituximab.[70]

Involved-site radiotherapy (ISRT) alone or combined with a less aggressive induction regimen is also an option for patients with stage I or contiguous stage II (non-bulky) disease.[70]

Select patients (e.g., those with good performance status) with asymptomatic noncontiguous stage II (non-bulky) disease may undergo active surveillance.[70]

Cardiovascular complications (including hypertension; atrial fibrillation; and ventricular arrhythmias, with related sudden cardiac death) may occur with BTK inhibitor therapy.[187][188][189][190] See Complications for further details.

See local specialist protocol for dosing guidelines.

Primary options

acalabrutinib

and

bendamustine

and

rituximab

bendamustine

and

rituximab

VR-CAP

bortezomib

and

rituximab

and

cyclophosphamide

and

doxorubicin

and

prednisolone

R-CHOP

rituximab

and

cyclophosphamide

and

doxorubicin

and

vincristine

and

prednisolone

lenalidomide

and

rituximab

acalabrutinib

and

rituximab

mantle cell lymphoma without TP53 mutation; advanced disease: initial presentation, suitable for aggressive induction therapy and stem cell transplant

Back

Consider –

supportive care

Additional treatment recommended for SOME patients in selected patient group

Patients on high-dose cyclophosphamide should receive mesna to prevent haemorrhagic cystitis.[185]

Patients receiving R-CHOP should be considered for prophylactic granulocyte colony-stimulating factor (G-CSF) to prevent treatment-related neutropenia.[180][181][182]

Antimicrobial prophylaxis should be considered if patients have severe neutropenia (absolute neutrophil count <500 cells/microlitre [<0.5 × 10⁹/L]).[184]

1st line – induction therapy (aggressive)

Back

1st line –

induction therapy (aggressive)

Patients should be enroled in a clinical trial if possible.[70]

Initial treatment is typically given in phases (induction, consolidation, maintenance).

Aggressive induction therapy is recommended for patients with advanced disease (stage II [bulky]; stage III-IV) without TP53 mutations who are suitable for aggressive induction therapy and stem cell transplant.[70] Options include the following regimens.[70]

LyMA regimen: R-DHA (rituximab, dexamethasone, and cytarabine) plus a platinum agent (carboplatin, cisplatin, or oxaliplatin) followed by R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone).[70]

NORDIC regimen: dose-intensified R-CHOP (known as R-maxi-CHOP) alternating with rituximab plus high-dose cytarabine.[70]

Rituximab plus bendamustine followed by rituximab plus high-dose cytarabine.[70]

TRIANGLE regimen, comprising R-CHOP plus a covalent Bruton's tyrosine kinase (BTK) inhibitor (ibrutinib, acalabrutinib, or zanubrutinib) alternating with R-DHA plus a platinum agent (carboplatin, cisplatin, or oxaliplatin).[70]

R-hyper-CVAD (rituximab plus cyclophosphamide, vincristine, doxorubicin, and dexamethasone, alternating with methotrexate and cytarabine).[70]

RBAC500 regimen (rituximab, bendamustine, and cytarabine).[70]

See local specialist protocol for dosing guidelines.

Primary options

R-DHA + platinum agent

rituximab

and

dexamethasone

and

cytarabine

-- AND --

carboplatin

cisplatin

oxaliplatin

R-CHOP

rituximab

and

cyclophosphamide

and

doxorubicin

and

vincristine

and

prednisolone

NORDIC regimen

rituximab

and

cyclophosphamide

and

doxorubicin

and

vincristine

and

prednisolone

and

cytarabine

RBAC500 regimen

rituximab

and

bendamustine

and

cytarabine

TRIANGLE regimen

rituximab

and

cyclophosphamide

and

doxorubicin

and

vincristine

and

prednisolone

and

dexamethasone

and

cytarabine

-- AND --

ibrutinib

acalabrutinib

zanubrutinib

-- AND --

carboplatin

cisplatin

oxaliplatin

R-hyper-CVAD

rituximab

and

cyclophosphamide

and

vincristine

and

doxorubicin

and

dexamethasone

and

methotrexate

and

cytarabine

Consider – maintenance and/or consolidation therapy

Back

Consider –

maintenance and/or consolidation therapy

Additional treatment recommended for SOME patients in selected patient group

Maintenance therapy with a covalent Bruton's tyrosine kinase (BTK) inhibitor (ibrutinib, acalabrutinib, or zanubrutinib) plus rituximab is recommended if patients achieve a complete response after aggressive induction therapy.[70]

Consolidation therapy with autologous stem cell transplant (followed by maintenance therapy with a covalent BTK inhibitor plus rituximab) is also an option if patients achieve a complete response after aggressive induction therapy.[70] Interim analysis of results from a phase 3 randomised trial suggest that patients who achieve complete remission with undetectable minimal residual disease after induction therapy may be less likely to benefit from consolidation autologous stem cell transplant in first remission.[149]

See local specialist protocol for dosing guidelines.

Primary options

ibrutinib

acalabrutinib

zanubrutinib

-- AND --

rituximab

mantle cell lymphoma without TP53 mutation; advanced disease: initial presentation, not suitable for aggressive induction therapy and stem cell transplant

Back

Consider –

supportive care

Additional treatment recommended for SOME patients in selected patient group

Patients on high-dose cyclophosphamide should receive mesna to prevent haemorrhagic cystitis.[185]

Patients receiving R-CHOP should be considered for prophylactic granulocyte colony-stimulating factor (G-CSF) to prevent treatment-related neutropenia.[180][181][182]

Antimicrobial prophylaxis should be considered if patients have severe neutropenia (absolute neutrophil count <500 cells/microlitre [<0.5 × 10⁹/L]).[184]

1st line – induction therapy (less aggressive)

Back

1st line –

induction therapy (less aggressive)

Patients should be enrolled in a clinical trial if possible.[70]

Initial treatment is typically given in phases (induction, consolidation, maintenance).

Less aggressive induction therapy is recommended for patients with advanced disease (stage II [bulky]; stage III-IV) without TP53 mutations who are not suitable for aggressive induction therapy.[70] Options include: acalabrutinib (a Bruton's tyrosine kinase [BTK] inhibitor) plus bendamustine plus rituximab; bendamustine plus rituximab; VR-CAP (bortezomib, rituximab, cyclophosphamide, doxorubicin, and prednisolone); R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone); lenalidomide plus rituximab; acalabrutinib plus rituximab.[70]

See local specialist protocol for dosing guidelines.

Primary options

acalabrutinib

and

bendamustine

and

rituximab

bendamustine

and

rituximab

VR-CAP

bortezomib

and

rituximab

and

cyclophosphamide

and

doxorubicin

and

prednisolone

R-CHOP

rituximab

and

cyclophosphamide

and

doxorubicin

and

vincristine

and

prednisolone

lenalidomide

and

rituximab

acalabrutinib

and

rituximab

Consider – maintenance therapy

Back

Consider –

maintenance therapy

Additional treatment recommended for SOME patients in selected patient group

Maintenance therapy with rituximab is recommended for patients who are in remission after induction therapy with bendamustine plus rituximab or R-CHOP, and who are not candidates for autologous stem cell transplant.[70]

See local specialist protocol for dosing guidelines.

Primary options

rituximab

mantle cell lymphoma with TP53 mutation: initial presentation

Back

Consider –

supportive care

Additional treatment recommended for SOME patients in selected patient group

Patients on high-dose cyclophosphamide should receive mesna to prevent haemorrhagic cystitis.[185]

Patients receiving R-CHOP should be considered for prophylactic granulocyte colony-stimulating factor (G-CSF) to prevent treatment-related neutropenia.[180][181][182]

Antimicrobial prophylaxis should be considered if patients have severe neutropenia (absolute neutrophil count <500 cells/microlitre [<0.5 × 10⁹/L]).[184]

1st line – induction therapy

Back

1st line –

induction therapy

Patients with TP53-mutated mantle cell lymphoma (MCL) treated with conventional MCL therapy (including autologous stem cell transplant [ASCT]) have a poor prognosis.[150][151]

Enrolment in a clinical trial is strongly recommended.[70]

In the absence of a suitable clinical trial, treatment with zanubrutinib plus obinutuzumab plus venetoclax can be considered for all patients with TP53-mutated MCL.

The TRIANGLE regimen, comprising R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) plus a covalent Bruton's tyrosine kinase (BTK) inhibitor (ibrutinib, acalabrutinib, or zanubrutinib) alternating with R-DHA [rituximab, dexamethasone, and cytarabine] plus a platinum agent (carboplatin, cisplatin, or oxaliplatin), can be considered for patients with TP53-mutated MCL who are suitable for aggressive induction therapy.

Less aggressive induction therapy (including acalabrutinib plus bendamustine plus rituximab; bendamustine plus rituximab; VR-CAP [bortezomib, rituximab, cyclophosphamide, doxorubicin, and prednisolone]; R-CHOP; lenalidomide plus rituximab; or acalabrutinib plus rituximab) can be considered for patients with TP53-mutated MCL who are not suitable for aggressive induction therapy.[70]

See local specialist protocol for dosing guidelines.

Primary options

zanubrutinib

and

obinutuzumab

and

venetoclax

TRIANGLE regimen

rituximab

and

cyclophosphamide

and

doxorubicin

and

vincristine

and

prednisolone

and

dexamethasone

and

cytarabine

-- AND --

ibrutinib

acalabrutinib

zanubrutinib

-- AND --

carboplatin

cisplatin

oxaliplatin

acalabrutinib

and

bendamustine

and

rituximab

bendamustine

and

rituximab

VR-CAP

bortezomib

and

rituximab

and

cyclophosphamide

and

doxorubicin

and

prednisolone

R-CHOP

rituximab

and

cyclophosphamide

and

doxorubicin

and

vincristine

and

prednisolone

lenalidomide

and

rituximab

acalabrutinib

and

rituximab

Consider – maintenance therapy

Back

Consider –

maintenance therapy

Additional treatment recommended for SOME patients in selected patient group

Maintenance therapy with a covalent Bruton's tyrosine kinase (BTK) inhibitor (ibrutinib, acalabrutinib, or zanubrutinib) plus rituximab is recommended after aggressive induction therapy with the TRIANGLE regimen.[70]

See local specialist protocol for dosing guidelines.

Primary options

ibrutinib

acalabrutinib

zanubrutinib

-- AND --

rituximab

mantle cell lymphoma: relapsed or refractory disease

Back

Consider –

supportive care

Additional treatment recommended for SOME patients in selected patient group

Patients on high-dose cyclophosphamide should receive mesna to prevent haemorrhagic cystitis.[185]

Patients receiving R-CHOP should be considered for prophylactic granulocyte colony-stimulating factor (G-CSF) to prevent treatment-related neutropenia.[180][181][182]

Antimicrobial prophylaxis should be considered if patients have severe neutropenia (absolute neutrophil count <500 cells/microlitre [<0.5 × 10⁹/L]).[184]

1st line – Bruton's tyrosine kinase (BTK) inhibitor, or lenalidomide + rituximab, or chimeric antigen receptor (CAR) T-cell therapy, or glofitamab

Back

1st line –

Bruton's tyrosine kinase (BTK) inhibitor, or lenalidomide + rituximab, or chimeric antigen receptor (CAR) T-cell therapy, or glofitamab

Although mantle cell lymphoma (MCL) is initially responsive to chemotherapy, the disease inevitably relapses.[152][153]Lenz G, Dreyling M, Hoster E, et al. Immunochemotherapy with rituximab and cyclophosphamide, doxorubicin, vincristine, and prednisone significantly improves response and time to treatment failure, but not long-term outcome in patients with previously untreated mantle cell lymphoma: results of a prospective randomized trial of the German Low Grade Lymphoma Study Group (GLSG). J Clin Oncol. 2005 Mar 20;23(9):1984-92.[154][155]

Preferred second-line treatments include: covalent BTK inhibitors (acalabrutinib; zanubrutinib), and lenalidomide plus rituximab.[70][156][157][158]

In 2023, the manufacturer of ibrutinib (a covalent BTK inhibitor) voluntarily withdrew the US indication for MCL after a confirmatory phase 3 trial in patients with untreated MCL failed to demonstrate significant improvement in overall survival and complete response rate compared with placebo (despite meeting its primary endpoint of progression-free survival).[159] In Europe, ibrutinib continues to be approved for use in patients with relapsed or refractory MCL.

For patients with relapsed or refractory disease after two or more lines of systemic therapy (including a covalent BTK inhibitor), options include: CAR T-cell therapy (brexucabtagene autoleucel; lisocabtagene maraleucel), pirtobrutinib (a non-covalent [reversible] BTK inhibitor), or glofitamab (a bispecific antibody therapy; if progressive disease occurs after CAR T-cell therapy and pirtobrutinib, or if ineligible for CAR T-cell therapy).[70][160][161]

See local specialist protocol for dosing guidelines.

Primary options

acalabrutinib

ibrutinib

zanubrutinib

lenalidomide

and

rituximab

Secondary options

brexucabtagene autoleucel

lisocabtagene maraleucel

pirtobrutinib

glofitamab

high-grade B-cell lymphoma, not otherwise specified (NOS); double-hit lymphoma or triple hit lymphoma

Back

Consider –

supportive care

Additional treatment recommended for SOME patients in selected patient group

Antimicrobial prophylaxis should be considered if patients have severe neutropenia (absolute neutrophil count <500 cells/microlitre [<0.5 × 10⁹/L]).[184]

1st line – R-EPOCH or R-CHOP-21 or R-mini-CHOP

Back

1st line –

R-EPOCH or R-CHOP-21 or R-mini-CHOP

High-grade B-cell lymphoma NOS appears blastoid or is intermediate between diffuse large B-cell lymphoma (DLBCL) and Burkitt's lymphoma, and lacks MYC and BCL2 rearrangements with or without BCL6 rearrangements.

High-grade B-cell lymphomas with rearrangements of MYC and BCL2 or BCL6 are known as 'double-hit' lymphomas; if all three are rearranged, they are referred to as 'triple-hit' lymphomas.

The optimal treatment approach for patients with high-grade B-cell lymphoma (NOS, double-hit, or triple-hit) has not been established. Enrolment in a clinical trial is recommended.[70]

The following rituximab-based chemotherapy regimens may be used for induction therapy: dose-adjusted R-EPOCH (rituximab plus etoposide, prednisolone, vincristine, cyclophosphamide, and doxorubicin); R-CHOP-21 (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone given on day 1 of a 21-day cycle), for patients with low risk or limited-stage disease (International Prognostic Index [IPI] <2); or R-mini-CHOP (rituximab plus reduced-dose CHOP), for patients who are frail or older.[70]

Consolidative involved-site radiotherapy (ISRT) is preferred for localised disease.[70]

See local specialist protocol for dosing guidelines.

Primary options

R-EPOCH

rituximab

and

etoposide

and

prednisolone

and

vincristine

and

cyclophosphamide

and

doxorubicin

R-CHOP

rituximab

and

cyclophosphamide

and

doxorubicin

and

vincristine

and

prednisolone

Back

Consider –

supportive care

Additional treatment recommended for SOME patients in selected patient group

Patients on high-dose cyclophosphamide should receive mesna to prevent haemorrhagic cystitis.[185]

Antimicrobial prophylaxis should be considered if patients have severe neutropenia (absolute neutrophil count <500 cells/microlitre [<0.5 × 10⁹/L]).[184]

peripheral T-cell lymphomas: initial presentation

Back

Consider –

CNS prophylaxis

Additional treatment recommended for SOME patients in selected patient group

Patients with high-grade B-cell lymphoma (NOS, double-hit, or triple-hit) are at risk for central nervous system (CNS) involvement.[162][163]

CNS prophylaxis can be considered in select cases with careful balancing of risk versus benefit. However, there are no robust data to support routine CNS prophylaxis, even among high-risk patients, and it is unclear if any prophylactic therapies effectively reduce the risk of CNS relapse. The optimal approach to CNS prophylaxis is unclear.

CNS prophylaxis may include systemic high-dose methotrexate and/or intrathecal methotrexate and/or intrathecal cytarabine, given during or after treatment.

See local specialist protocol for dosing guidelines.

Primary options

methotrexate

and/or

cytarabine

aggressive T-cell lymphomas

1st line – brentuximab vedotin + CHP, or CHOEP, or CHOP, or EPOCH

Back

1st line –

brentuximab vedotin + CHP, or CHOEP, or CHOP, or EPOCH

Peripheral T-cell lymphomas (PTCLs) comprise: PTCL not otherwise specified (PTCL NOS); nodal T-follicular helper cell lymphomas (nTFHLs); systemic anaplastic large cell lymphoma (systemic ALCL); enteropathy-associated T-cell lymphoma (EATL); monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL).

Treatment for PTCLs is based on histopathology (e.g., CD30 expression), stage, and patient factors (e.g., age, fitness, comorbidities).[164]

Patients with PTCLs (except those with ALK-positive ALCL) are often unsuitable for chemotherapy and have a poor prognosis because of older age and poor performance status at diagnosis.[165][166]

A clinical trial is preferred for most patients with PTCL.

In the absence of a suitable clinical trial, or if a patient has ALK-positive ALCL, the following regimens can be used for first-line treatment: brentuximab vedotin plus CHP (cyclophosphamide, doxorubicin, and prednisolone) if CD30-positive histology confirmed; CHOEP (cyclophosphamide, doxorubicin, vincristine, etoposide, prednisolone); CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone); dose-adjusted EPOCH (etoposide, prednisolone, vincristine, cyclophosphamide, doxorubicin).[71]

Patients who are unfit for chemotherapy are managed with the aim of palliation of symptoms.

See local specialist protocol for dosing guidelines.

Primary options

Brentuximab vedotin + CHP

brentuximab vedotin

and

cyclophosphamide

and

doxorubicin

and

prednisolone

CHOEP

cyclophosphamide

and

doxorubicin

and

vincristine

and

etoposide

and

prednisolone

CHOP

cyclophosphamide

and

doxorubicin

and

vincristine

and

prednisolone

EPOCH

etoposide

and

prednisolone

and

vincristine

and

cyclophosphamide

and

doxorubicin

Consider – radiotherapy

Back

Consider –

radiotherapy

Additional treatment recommended for SOME patients in selected patient group

Involved-site radiotherapy (ISRT) may be combined with first-line treatment regimens.[71]

Chemotherapy alone is, however, recommended for patients with stage III-IV ALK-positive anaplastic large cell lymphoma (ALCL).

Consider – autologous stem cell transplant

Back

Consider –

autologous stem cell transplant

Additional treatment recommended for SOME patients in selected patient group

Eligible patients in complete remission following initial therapy may be considered for autologous stem cell transplant (ASCT).[71][167] However, the benefits of ASCT in peripheral T-cell lymphoma are unclear, and may be limited to certain subtypes.[168][169][170][171]

peripheral T-cell lymphomas: relapsed or refractory disease

Back

Consider –

supportive care

Additional treatment recommended for SOME patients in selected patient group

Patients on high-dose cyclophosphamide should receive mesna to prevent haemorrhagic cystitis.[185]

Mesna is not required for less intensive cyclophosphamide-containing regimens (e.g., CHOP [cyclophosphamide, doxorubicin, vincristine, prednisolone], CHOEP [cyclophosphamide, doxorubicin, vincristine, etoposide, prednisolone]).

Antimicrobial prophylaxis should be considered if patients have severe neutropenia (absolute neutrophil count <500 cells/microlitre [<0.5 × 10⁹/L]).[184]

1st line – targeted therapy

Back

1st line –

targeted therapy

Recommended second-line and subsequent treatments for patients with PTCL who have relapsed or refractory disease include: belinostat, brentuximab vedotin (if not used previously and CD30-positive histology confirmed), duvelisib, pralatrexate, romidepsin, or ALK inhibitors for ALK-positive ALCL (e.g., alectinib, brigatinib, ceritinib, crizotinib, lorlatinib).[71]

See local specialist protocol for dosing guidelines.

Primary options

belinostat

brentuximab vedotin

duvelisib

pralatrexate

romidepsin

alectinib

brigatinib

ceritinib

crizotinib

lorlatinib

subcutaneous panniculitis-like peripheral T-cell lymphoma; with haemophagocytic lymphohistiocytosis, systemic disease, or high tumour burden

Back

Consider –

supportive care

Additional treatment recommended for SOME patients in selected patient group

Antimicrobial prophylaxis should be considered if patients have severe neutropenia (absolute neutrophil count <500 cells/microlitre [<0.5 × 10⁹/L]).[184]

1st line – ciclosporin ± prednisolone, or pralatrexate ± prednisolone, or romidepsin ± prednisolone, or CHOEP, or EPOCH, or ESHA + cisplatin or oxaliplatin, or ICE

Back

1st line –

ciclosporin ± prednisolone, or pralatrexate ± prednisolone, or romidepsin ± prednisolone, or CHOEP, or EPOCH, or ESHA + cisplatin or oxaliplatin, or ICE

Optimal management of subcutaneous panniculitis-like peripheral T-cell lymphoma (SPTCL) is unclear.

Treatment can be guided by the presence of haemophagocytic lymphohistiocytosis (HLH) and tumour burden.[80]

The following regimens can be considered for first-line treatment of patients with HLH, systemic disease, or high tumour burden: ciclosporin (with or without prednisolone); pralatrexate (with or without prednisolone); romidepsin (with or without prednisolone); CHOEP (cyclophosphamide, doxorubicin, vincristine, etoposide, prednisolone); dose-adjusted EPOCH (etoposide, prednisolone, vincristine, cyclophosphamide, and doxorubicin); ESHA (etoposide, methylprednisolone, cytarabine) plus a platinum agent (cisplatin or oxaliplatin); or ICE (ifosfamide, carboplatin, and etoposide).[80]

See local specialist protocol for dosing guidelines.

Primary options

ciclosporin

and

prednisolone

pralatrexate

and

prednisolone

romidepsin

and

prednisolone

CHOEP

cyclophosphamide

and

doxorubicin

and

vincristine

and

etoposide

and

prednisolone

EPOCH

etoposide

and

prednisolone

and

vincristine

and

cyclophosphamide

and

doxorubicin

ESHA + platinum agent

etoposide

and

methylprednisolone

and

cytarabine

-- AND --

cisplatin

oxaliplatin

ICE

ifosfamide

and

carboplatin

and

etoposide

subcutaneous panniculitis-like peripheral T-cell lymphoma; without haemophagocytic lymphohistiocytosis, and low tumour burden (localised or limited subcutaneous disease)

Back

Consider –

supportive care

Additional treatment recommended for SOME patients in selected patient group

Patients on high-dose cyclophosphamide or ifosfamide should receive mesna to prevent haemorrhagic cystitis.[185]

Antimicrobial prophylaxis should be considered if patients have severe neutropenia (absolute neutrophil count <500 cells/microlitre [<0.5 × 10⁹/L]).[184]

1st line – ciclosporin ± prednisolone, or methotrexate ± prednisolone, or bexarotene ± prednisolone, or local therapy

Back

1st line –

ciclosporin ± prednisolone, or methotrexate ± prednisolone, or bexarotene ± prednisolone, or local therapy

Optimal management of subcutaneous panniculitis-like peripheral T-cell lymphoma (SPTCL) is unclear.

Treatment can be guided by the presence of haemophagocytic lymphohistiocytosis (HLH) and tumour burden.[80]

The following options can be considered for first-line treatment for patients without HLH who have low tumour burden (localised or limited subcutaneous disease): ciclosporin (with or without prednisolone); methotrexate (with or without prednisolone); bexarotene (with or without prednisolone); or local therapy (involved-site radiotherapy [ISRT] or intralesional corticosteroid).[80]

See local specialist protocol for dosing guidelines.

Primary options

ciclosporin

and

prednisolone

methotrexate

and

prednisolone

bexarotene

and

prednisolone

classic follicular lymphoma; stage I or II: initial presentation

Back

Consider –

supportive care

Additional treatment recommended for SOME patients in selected patient group

Antimicrobial prophylaxis should be considered if patients have severe neutropenia (absolute neutrophil count <500 cells/microlitre [<0.5 × 10⁹/L]).[184]

indolent B-cell lymphomas

1st line – active surveillance, or radiotherapy, or rituximab

Back

1st line –

active surveillance, or radiotherapy, or rituximab

Treatment for classic follicular lymphoma is based on stage, indications for treatment (including: symptoms; threatened end-organ function; clinically significant/progressive cytopenia secondary to lymphoma; clinically significant bulky disease; steady/rapid progression), and patient factors (e.g., age, fitness, comorbidities).[70]

Prognostic tools (e.g., Groupe d'Etude des Lymphomes Folliculaires [GELF] criteria or Follicular Lymphoma International Prognostic Index [FLIPI]) can help guide treatment. See Criteria.

Initial therapy for localised (stage I or II) disease includes involved-site radiotherapy and/or rituximab (with or without chemotherapy depending on tumour burden).[70]

Active surveillance may be considered for some patients (e.g., those with noncontiguous stage II disease in whom toxicity of treatment outweighs benefit).[70]

See local specialist protocol for dosing guidelines.

Primary options

rituximab

classic follicular lymphoma; stage III or IV: initial presentation

Back

Consider –

supportive care

Additional treatment recommended for SOME patients in selected patient group

Antimicrobial prophylaxis should be considered if patients have severe neutropenia (absolute neutrophil count <500 cells/microlitre [<0.5 × 10⁹/L]).[184]

1st line – active surveillance, or rituximab, or chemotherapy ± rituximab or obinutuzumab, or lenalidomide + rituximab

Back

1st line –

active surveillance, or rituximab, or chemotherapy ± rituximab or obinutuzumab, or lenalidomide + rituximab

Active surveillance is recommended for patients with advanced-stage disease (stage III or IV) who have no indication for treatment.[70]

For patients with advanced-stage disease who have a high tumour burden and indications for treatment, the preferred first-line treatment regimens include: CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) plus obinutuzumab or rituximab; bendamustine plus rituximab or obinutuzumab; CVP (cyclophosphamide, vincristine, and prednisolone) plus obinutuzumab or rituximab; or lenalidomide plus rituximab.[70][172][173][174][175]

The preferred first-line treatment for patients with low tumour burden and indications for treatment is rituximab alone.[70]

The preferred first-line treatment for patients who are older or who have significant comorbidities is rituximab alone.[70] Chlorambucil (with or without rituximab) or cyclophosphamide (with or without rituximab) may also be considered for these patients.

Consolidation with rituximab may be considered for patients with stage III or IV disease who respond to initial treatment with rituximab alone.[70]

Maintenance therapy with rituximab or obinutuzumab may be considered for patients with stage III or IV disease who respond to chemoimmunotherapy (depending on the initial regimen used and response achieved).[70]

See local specialist protocol for dosing guidelines.

Primary options

rituximab

obinutuzumab

and

cyclophosphamide

and

doxorubicin

and

vincristine

and

prednisolone

rituximab

and

cyclophosphamide

and

doxorubicin

and

vincristine

and

prednisolone

bendamustine

and

rituximab

bendamustine

and

obinutuzumab

lenalidomide

and

rituximab

obinutuzumab

and

cyclophosphamide

and

vincristine

and

prednisolone

rituximab

and

cyclophosphamide

and

vincristine

and

prednisolone

chlorambucil

and

rituximab

cyclophosphamide

and

rituximab

classic follicular lymphoma; relapsed/progressive/refractory disease

Back

Consider –

supportive care

Additional treatment recommended for SOME patients in selected patient group

Antimicrobial prophylaxis should be considered if patients have severe neutropenia (absolute neutrophil count <500 cells/microlitre [<0.5 × 10⁹/L]).[184]

1st line – active surveillance, or chemotherapy, or targeted therapy, or immunotherapy

Back

1st line –

active surveillance, or chemotherapy, or targeted therapy, or immunotherapy

Patients with relapsed or progressive disease who have no indications for treatment can undergo active surveillance.[70]

Second-line treatments can be considered for patients with relapsed, progressive, or refractory disease who have indications for treatment.[70]

Second-line options include (if not used previously): CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone) plus obinutuzumab or rituximab; CVP (cyclophosphamide, vincristine, and prednisolone) plus obinutuzumab or rituximab; bendamustine plus obinutuzumab or rituximab; tafasitamab plus lenalidomide plus rituximab (if the patient has received ≥1 prior systemic therapy including anti-CD20 monoclonal antibody therapy [e.g., rituximab, obinutuzumab]); lenalidomide with or without rituximab; lenalidomide plus obinutuzumab; obinutuzumab alone; rituximab alone.[70]

Preferred second-line treatment for patients who are older or who have significant comorbidities is rituximab alone or tazemetostat.[70] Cyclophosphamide (with or without rituximab) may also be considered for these patients.

Maintenance therapy with rituximab or obinutuzumab, or consolidation therapy with autologous stem cell transplant (ASCT), may be considered for those who respond to second-line treatment.[70]

Third-line and subsequent treatment options include: bispecific antibody therapy (epcoritamab; mosunetuzumab); CAR T-cell therapy (axicabtagene ciloleucel; lisocabtagene maraleucel; tisagenlecleucel); tazemetostat; zanubrutinib plus obinutuzumab; or loncastuximab tesirine plus rituximab.

Second-line treatments can also be considered for third-line use if not previously used.

See local specialist protocol for dosing guidelines.

Primary options

obinutuzumab

and

cyclophosphamide

and

doxorubicin

and

vincristine

and

prednisolone

rituximab

and

cyclophosphamide

and

doxorubicin

and

vincristine

and

prednisolone

obinutuzumab

and

cyclophosphamide

and

vincristine

and

prednisolone

rituximab

and

cyclophosphamide

and

vincristine

and

prednisolone

bendamustine

and

obinutuzumab

bendamustine

and

rituximab

tafasitamab

and

lenalidomide

and

rituximab

lenalidomide

and

rituximab

lenalidomide

and

obinutuzumab

rituximab

tazemetostat

cyclophosphamide

and

rituximab

Secondary options

tisagenlecleucel

lisocabtagene maraleucel

axicabtagene ciloleucel

epcoritamab

mosunetuzumab

zanubrutinib

and

obinutuzumab

loncastuximab tesirine

and

rituximab

marginal zone lymphoma; nodal

Back

Consider –

supportive care

Additional treatment recommended for SOME patients in selected patient group

Patients on high-dose cyclophosphamide should receive mesna to prevent haemorrhagic cystitis.[185]

Antimicrobial prophylaxis should be considered if patients have severe neutropenia (absolute neutrophil count <500 cells/microlitre [<0.5 × 10⁹/L]).[184]

1st line – active surveillance, or radiotherapy, or chemotherapy and/or immunotherapy

Back

1st line –

active surveillance, or radiotherapy, or chemotherapy and/or immunotherapy

Treatment for nodal marginal zone lymphoma (MZL) is based on stage, indications for treatment, and patient factors.

The treatment approach and treatment options for nodal MZL are broadly the same as classic follicular lymphoma.[70]

marginal zone lymphoma; splenic: initial presentation

1st line – hepatitis C treatment, or rituximab, or splenectomy, or active surveillance, or observation

Back

1st line –

hepatitis C treatment, or rituximab, or splenectomy, or active surveillance, or observation

Treatment for splenic marginal zone lymphoma (MZL) is informed by the presence of splenomegaly, indications for treatment (e.g., symptoms; threatened end-organ function; cytopenias [including autoimmune cytopenia]; clinically significant bulky disease; steady or rapid progression), hepatitis C status, and patient factors.[70]

Patients who are asymptomatic with no splenomegaly or progressive cytopenias can be observed until indications for treatment develop.[70]

Patients with splenomegaly should be treated according to hepatitis C status.[70] Options include: hepatitis C treatment (if hepatitis C positive); active surveillance (if hepatitis C negative and asymptomatic); rituximab (if hepatitis C negative, and cytopenias or symptoms are present); or splenectomy (in select hepatitis C-negative patients with cytopenias or symptoms or who are not responsive to rituximab).[70]

For detailed information on hepatitis C treatment, see Hepatitis C topic.

See local specialist protocol for dosing guidelines.

Primary options

rituximab

marginal zone lymphoma; splenic: relapsed disease

Back

Consider –

supportive care

Additional treatment recommended for SOME patients in selected patient group

Antimicrobial prophylaxis should be considered if patients have severe neutropenia (absolute neutrophil count <500 cells/microlitre [<0.5 × 10⁹/L]).[184]

1st line – active surveillance, or systemic therapy, or splenectomy, or palliative radiotherapy

Back

1st line –

active surveillance, or systemic therapy, or splenectomy, or palliative radiotherapy

Patients with splenic marginal zone lymphoma (MZL) who relapse should undergo active surveillance if they have no indications for treatment.[70]

Systemic therapy, splenectomy, or palliative involved-site radiotherapy (ISRT) is recommended for patients with splenic MZL who relapse and have indications for treatment.[70]

Systemic therapy includes (if not used previously): rituximab; bendamustine plus obinutuzumab; bendamustine plus rituximab; acalabrutinib; zanubrutinib (after at least one prior anti-CD20 monoclonal antibody-based regimen); ibrutinib; pirtobrutinib (after prior covalent Bruton's tyrosine kinase [BTK] inhibitor therapy [e.g., acalabrutinib, zanubrutinib, ibrutinib]); R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone); R-CVP (rituximab, cyclophosphamide, vincristine, prednisolone); lenalidomide plus rituximab; lenalidomide plus obinutuzumab.[70]

Axicabtagene ciloleucel (a chimeric antigen receptor [CAR] T-cell therapy) can be considered for subsequent systemic therapy.[70]

See local specialist protocol for dosing guidelines.

Primary options

rituximab

bendamustine

and

obinutuzumab

bendamustine

and

rituximab

acalabrutinib

zanubrutinib

ibrutinib

pirtobrutinib

R-CHOP

rituximab

and

cyclophosphamide

and

doxorubicin

and

vincristine

and

prednisolone

R-CVP

rituximab

and

cyclophosphamide

and

vincristine

and

prednisolone

lenalidomide

and

rituximab

lenalidomide

and

obinutuzumab

Secondary options

axicabtagene ciloleucel

primary cutaneous B-cell lymphoma (primary cutaneous follicle centre lymphoma and primary cutaneous marginal zone lymphoma)

Back

Consider –

supportive care

Additional treatment recommended for SOME patients in selected patient group

Patients on high-dose cyclophosphamide should receive mesna to prevent haemorrhagic cystitis.[185]

Patients receiving R-CHOP should be considered for prophylactic granulocyte colony-stimulating factor (G-CSF) to prevent treatment-related neutropenia.[180][181][182]

Antimicrobial prophylaxis should be considered if patients have severe neutropenia (absolute neutrophil count <500 cells/microlitre [<0.5 × 10⁹/L]).[184]

1st line – surgery, or radiotherapy, or rituximab ± chemotherapy, or observation

Back

1st line –

surgery, or radiotherapy, or rituximab ± chemotherapy, or observation

Treatment options for localised primary cutaneous follicle centre lymphoma (PCFCL) and primary cutaneous marginal zone lymphoma (PCMZL) include: local involved-site radiotherapy (ISRT; preferred); or surgical resection (for small isolated lesions); or observation (if ISRT or surgical resection is neither feasible nor desired).[80]

Patients with generalised disease or cosmetically disfiguring lesions may be managed with the treatment options recommended for localised PCFCL and PCMZL. Observation is appropriate for asymptomatic patients with generalised disease. Consider systemic treatment (e.g., rituximab with or without CHOP [cyclophosphamide, doxorubicin, vincristine, and prednisolone]) for patients with extensive generalised disease.[80]

See local specialist protocol for dosing guidelines.

Primary options

rituximab

R-CHOP

rituximab

and

cyclophosphamide

and

doxorubicin

and

vincristine

and

prednisolone

primary cutaneous B-cell lymphoma (primary cutaneous diffuse large B-cell lymphoma, leg type)

Back

Consider –

supportive care

Additional treatment recommended for SOME patients in selected patient group

Patients on high-dose cyclophosphamide should receive mesna to prevent haemorrhagic cystitis.[185]

Patients receiving R-CHOP should be considered for prophylactic granulocyte colony-stimulating factor (G-CSF) to prevent treatment-related neutropenia.[180][181][182]

Antimicrobial prophylaxis should be considered if patients have severe neutropenia (absolute neutrophil count <500 cells/microlitre [<0.5 × 10⁹/L]).[184]

1st line – R-CHOP ± radiotherapy, or radiotherapy alone

Back

1st line –

R-CHOP ± radiotherapy, or radiotherapy alone

Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL, leg type) is associated with an aggressive clinical course and poor survival.

Recommended first-line treatments for patients with PCDLBCL, leg type include: R-CHOP plus local involved-site radiotherapy (ISRT) for localised disease; or local ISRT alone (for localised disease if unable to tolerate chemoimmunotherapy); or R-CHOP with or without local ISRT for generalised disease.[70]

See local specialist protocol for dosing guidelines.

Primary options

R-CHOP

rituximab

and

cyclophosphamide

and

doxorubicin

and

vincristine

and

prednisolone

Back

Consider –

CNS prophylaxis

Additional treatment recommended for SOME patients in selected patient group

CNS prophylaxis may be considered for patients with PCDLBCL, leg type due to the increased risk for CNS relapse with this subtype.[70][176]

See local specialist protocol for dosing guidelines.

Primary options

methotrexate

and/or

cytarabine

primary cutaneous anaplastic large cell lymphoma; with solitary or grouped lesions

Back

Consider –

supportive care

Additional treatment recommended for SOME patients in selected patient group

Patients on high-dose cyclophosphamide should receive mesna to prevent haemorrhagic cystitis.[185]

Patients receiving R-CHOP should be considered for prophylactic granulocyte colony-stimulating factor (G-CSF) to prevent treatment-related neutropenia.[180][181][182]

Antimicrobial prophylaxis should be considered if patients have severe neutropenia (absolute neutrophil count <500 cells/microlitre [<0.5 × 10⁹/L]).[184]

indolent T-cell lymphomas

1st line – radiotherapy, or surgical excision ± radiotherapy

Back

1st line –

radiotherapy, or surgical excision ± radiotherapy

Treatments for localised disease (solitary or grouped lesions) include involved-site radiotherapy (ISRT), or surgical excision with or without ISRT (for small local lesions).[80]

primary cutaneous anaplastic large cell lymphoma; with multifocal lesions or regional lymph node involvement

1st line – brentuximab vedotin

Back

1st line –

brentuximab vedotin

Brentuximab vedotin is the preferred initial treatment for patients with multifocal lesions or regional lymph node involvement.[80]

See local specialist protocol for dosing guidelines.

Primary options

brentuximab vedotin

Consider – radiotherapy

Back

Consider –

radiotherapy

Additional treatment recommended for SOME patients in selected patient group

Involved-site radiotherapy (ISRT) may be combined with brentuximab vedotin, or used alone, in select patients with regional lymph node involvement.[80]

breast implant-associated anaplastic large cell lymphoma; localised disease

Back

Consider –

supportive care

Additional treatment recommended for SOME patients in selected patient group

Antimicrobial prophylaxis should be considered if patients have severe neutropenia (absolute neutrophil count <500 cells/microlitre [<0.5 × 10⁹/L]).[184]

1st line – surgery

Back

1st line –

surgery

Treatment for localised disease (i.e., confined to the fibrous scar capsule) is complete surgical resection of the breast implant, capsule, and associated mass.[71] Suspicious lymph nodes detected during explantation should be biopsied.

Removal of the contralateral breast implant can be considered; bilateral disease is reported in approximately 4.6% of cases.[71][177]

Re-excision surgery alone (without systemic therapy) may be possible for local disease relapse.[71]

The US Food and Drug Administration (FDA) recommends that cases of breast implant-associated anaplastic large cell lymphoma should be reported to a national disease registry (e.g., PROFILE Registry).[179]

breast implant-associated anaplastic large cell lymphoma; unresectable breast mass or advanced disease

1st line – brentuximab vedotin with or without CHP, or CHOP, or CHOEP, or EPOCH

Back

1st line –

brentuximab vedotin with or without CHP, or CHOP, or CHOEP, or EPOCH

Patients with breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) who present with an unresectable breast mass or those with extended disease (stage II to IV) may be considered for systemic therapy, including: brentuximab vedotin (an anti-CD30 antibody-drug conjugate) with or without CHP (cyclophosphamide, doxorubicin, and prednisolone); CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone); CHOEP (cyclophosphamide, doxorubicin, vincristine, etoposide, prednisolone); dose-adjusted EPOCH (etoposide, prednisolone, vincristine, cyclophosphamide, doxorubicin).[71]

Debulking surgery before systemic therapy may be considered for patients with disseminated stage IV disease, but this should be discussed with a multidisciplinary team.[178]

The US Food and Drug Administration (FDA) recommends that cases of BIA-ALCL should be reported to a national disease registry (e.g., PROFILE Registry).[179]

See local specialist protocol for dosing guidelines.

Primary options

brentuximab vedotin

Brentuximab vedotin + CHP

brentuximab vedotin

and

cyclophosphamide

and

doxorubicin

and

prednisolone

CHOP

cyclophosphamide

and

doxorubicin

and

vincristine

and

prednisolone

CHEOP

cyclophosphamide

and

doxorubicin

and

vincristine

and

etoposide

and

prednisolone

EPOCH

etoposide

and

prednisolone

and

vincristine

and

cyclophosphamide

and

doxorubicin