Classic Hodgkin lymphoma (HL) is a malignancy in which the patient's Reed–Sternberg cells are dispersed within an extensive inflammatory infiltrate. Owing to the increased expression of the immune checkpoint ligands PD-L1 and PD-L2 in classic HL, the combination of these factors sets the stage for this disease being responsive to therapeutic agents that target PD-1. Preliminary results have shown that nivolumab is efficacious in a number of haematological cancers, and this agent has already received FDA approval for several indications. The excitement surrounding these promising data prompted a phase Ib cohort study to asssess the safety and efficacy of pembrolizumab in patients with relapsed or refractory HL who had disease progression on prior treatment with brentuximab vendotin.

In total, 31 heavily pretreated patients were enrolled in the trial; over 50% had received five or more previous lines of therapy. At 24 weeks, the progression-free survival and overall survival rates for those treated with pembrolizumab were an impressive 69% and 100%, respectively. Importantly, response rates were lower in patients who had relapsed following transplantation, owing to the high disease burden and resistance in this population; however, these patients still derived treatment benefit. The toxicity profile was acceptable and in line with the adverse effects seen for pembrolizumab in patients with solid tumours.

tremendous clinical benefit...almost unheard of for patients with lymphoma

Craig Moskowitz, the senior author of the study report, highlights the key findings: “the prolonged responses and tremendous clinical benefit observed in this population in the palliative-care setting are almost unheard of for patients with lymphoma, with stable partial responses and complete responses beyond 2 years”. Moskowitz also comments that “longer-term use of this agent has provided even more encouraging ongoing durable responses and this agent will no doubt be fast-tracked for FDA approval.”