Emerging treatments

Venetoclax

Venetoclax is an oral B-cell lymphoma-2 (BCL-2) inhibitor. In a phase 2 trial of 30 patients with previously treated WM, venetoclax had an overall response rate of 87%.[109] Severe neutropenia occurred in 13.3% of patients.[109]

Daratumumab

Daratumumab is an anti-CD38 monoclonal antibody. It has been used extensively in multiple myeloma, and is undergoing clinical trials in WM given its likely efficacy and tolerability.[110][111]

Everolimus

Everolimus is a mammalian target of rapamycin (mTOR) inhibitor. In a phase 2 trial of 60 patients with relapsed/refractory WM, everolimus had an overall response rate of 50% (all were partial response), and median progression-free survival was 21 months.[112] In a phase 2 trial of 33 patients with symptomatic untreated WM, everolimus had an overall response rate of 72.7%.[113] Pneumonitis occurred in 6 patients, with 3 patients requiring hospitalization.[113]

Perifosine

Perifosine is a novel alkylphospholipid Akt inhibitor. In a phase 2 trial of 37 patients with relapsed/refractory WM, perifosine had a partial response rate of 11%.[114] Other studies have reported an overall response rate of 36%.[115]

Panobinostat

Panobinostat is a histone deacetylase (HDAC) inhibitor. In a phase 2 trial of 39 patients with relapsed/refractory WM, panobinostat had an overall response rate of 47%.[116]

Ofatumumab

Ofatumumab is a fully human anti-CD20 monoclonal antibody. In a phase 2 trial of 37 patients with WM (28 patients with relapsed/refractory WM), ofatumumab had an overall response rate of 32%.[117]

Pentostatin plus cyclophosphamide and rituximab

Pentostatin is an antimetabolite chemotherapy agent. In a phase 2 trial of 25 patients with WM, pentostatin plus cyclophosphamide and rituximab had a 2-year progression-free survival rate of 83.6% and a 2-year overall survival rate of 100% in those with untreated WM (n=21).[118]

Pirtobrutinib

Pirtoburinib, a noncovalent third-generation Bruton tyrosine kinase (BTK) inhibitor, has demonstrated promising activity and good tolerability in the phase 1/2 BRUIN trial of patients with relapsed low-grade B-cell non-Hodgkin lymphoma, that also included patients with relapsed WM previously treated with BTK inhibitors.[119] 

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