Immune checkpoint inhibitors (first-line setting)
Pembrolizumab and nivolumab are monoclonal antibodies that target the programmed death-1 (PD-1) receptor. Phase 2 trials investigating pembrolizumab or nivolumab in the first-line setting in patients with newly diagnosed classical HL have shown promising results.[142]Ramchandren R, Domingo-Domènech E, Rueda A, et al. Nivolumab for newly diagnosed advanced-stage classic Hodgkin lymphoma: safety and efficacy in the phase II CheckMate 205 study. J Clin Oncol. 2019 Aug 10;37(23):1997-2007.
https://www.doi.org/10.1200/JCO.19.00315
http://www.ncbi.nlm.nih.gov/pubmed/31112476?tool=bestpractice.com
[143]Bröckelmann PJ, Goergen H, Keller U, et al. Efficacy of nivolumab and AVD in early-stage unfavorable classic Hodgkin lymphoma: the randomized phase 2 German Hodgkin Study Group NIVAHL trial. JAMA Oncol. 2020 Jun 1;6(6):872-80.
https://www.doi.org/10.1001/jamaoncol.2020.0750
http://www.ncbi.nlm.nih.gov/pubmed/32352505?tool=bestpractice.com
[144]Allen PB, Savas H, Evens AM, et al. Pembrolizumab followed by AVD in untreated early unfavorable and advanced-stage classical Hodgkin lymphoma. Blood. 2021 Mar 11;137(10):1318-1326.
https://www.doi.org/10.1182/blood.2020007400
http://www.ncbi.nlm.nih.gov/pubmed/32992341?tool=bestpractice.com
Pembrolizumab and nivolumab are already approved for use in patients with refractory or relapsed classical HL. (See Management approach)
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 (panobinostat, entinostat, and mocetinostat) have demonstrated activity in patients with relapsed or refractory classical HL.[145]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
[146]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
[147]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
[148]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
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.[149]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
Camidanlumab tesirine
A phase 1 trial investigating camidanlumab tesirine (an anti-CD25 monoclonal antibody conjugated to pyrrolobenzodiazepine dimer toxin) in heavily pre-treated patients with relapsed or refractory HL reported an overall response rate of 71%.[150]Hamadani M, Collins GP, Caimi PF, et al. Camidanlumab tesirine in patients with relapsed or refractory lymphoma: a phase 1, open-label, multicentre, dose-escalation, dose-expansion study. Lancet Haematol. 2021 Jun;8(6):e433-45.
http://www.ncbi.nlm.nih.gov/pubmed/34048682?tool=bestpractice.com