Histone deacetylase (HDAC) inhibitors
HDAC inhibitors are epigenetic modifiers that can induce tumour cell apoptosis by blocking the activity of HDAC enzymes. Several HDAC inhibitors (e.g., panobinostat, entinostat, mocetinostat, vorinostat) have demonstrated activity in patients with relapsed or refractory classical HL.[137]Adams H, Obermann EC, Dirnhofer S, et al. Targetable molecular pathways in classical Hodgkin's lymphoma. Expert Opin Investig Drugs. 2011;20:141-151.
http://www.ncbi.nlm.nih.gov/pubmed/21204722?tool=bestpractice.com
[138]Younes A, Sureda A, Ben-Yehuda D, et al. Panobinostat in patients with relapsed/refractory Hodgkin's lymphoma after autologous stem-cell transplantation: results of a phase II study. J Clin Oncol. 2012 Jun 20;30(18):2197-203.
https://www.doi.org/10.1200/JCO.2011.38.1350
http://www.ncbi.nlm.nih.gov/pubmed/22547596?tool=bestpractice.com
[139]Batlevi CL, Kasamon Y, Bociek RG, et al. ENGAGE- 501: phase II study of entinostat (SNDX-275) in relapsed and refractory Hodgkin lymphoma. Haematologica. 2016 Aug;101(8):968-75.
https://www.doi.org/10.3324/haematol.2016.142406
http://www.ncbi.nlm.nih.gov/pubmed/27151994?tool=bestpractice.com
[140]Younes A, Oki Y, Bociek RG, et al. Mocetinostat for relapsed classical Hodgkin's lymphoma: an open-label, single-arm, phase 2 trial. Lancet Oncol. 2011 Dec;12(13):1222-8.
http://www.ncbi.nlm.nih.gov/pubmed/22033282?tool=bestpractice.com
[141]Janku F, Park H, Call SG, et al. Safety and efficacy of vorinostat plus sirolimus or everolimus in patients with relapsed refractory Hodgkin lymphoma. Clin Cancer Res. 2020 Nov 1;26(21):5579-87.
http://www.ncbi.nlm.nih.gov/pubmed/33055173?tool=bestpractice.com
HDAC inhibitors may enhance the activity of PD-1 blockade, suggesting a role for the addition of an HDAC inhibitor for patients with progression on PD-1 blockade.[142]Mei M, Chen L, Godfrey J, et al. Pembrolizumab plus vorinostat induces responses in patients with Hodgkin lymphoma refractory to prior PD-1 blockade. Blood. 2023 Oct 19;142(16):1359-70.
https://pmc.ncbi.nlm.nih.gov/articles/PMC11561539
http://www.ncbi.nlm.nih.gov/pubmed/37339586?tool=bestpractice.com
Chimeric antigen receptor (CAR) T-cell therapy
A phase 1/2 trial investigating CD30-directed CAR T-cell therapy in heavily pre-treated patients with relapsed or refractory CD30-positive HL reported a high rate of durable responses, particularly when lymphodepleting chemotherapy (e.g., cyclophosphamide and fludarabine) was given prior to CAR T-cell therapy.[143]Ramos CA, Grover NS, Beaven AW, et al. Anti-CD30 CAR-T cell therapy in relapsed and refractory Hodgkin lymphoma. J Clin Oncol. 2020 Nov 10;38(32):3794-804.
https://www.doi.org/10.1200/JCO.20.01342
http://www.ncbi.nlm.nih.gov/pubmed/32701411?tool=bestpractice.com