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Pembrolizumab (Keytruda) significantly improved progression-free survival (PFS) over brentuximab vedotin (Adcetris) for Hodgkin's lymphoma patients who failed on or were ineligible for transplant, findings from KEYNOTE-204 showed.

Among the 300 patients in the phase III trial, median PFS on blinded central review reached 13.2 months with the PD-1 immune checkpoint inhibitor pembrolizumab, as compared with 8.3 months with brentuximab vedotin, an antibody-drug conjugate (HR 0.65, 95% CI 0.48-0.88, P=0.0027), reported Pier Luigi Zinzani, MD, PhD, of the University of Bologna in Italy.

This nearly 5-month PFS benefit was "clinically meaningful," said Zinzani, and extended to key groups, including those with primary refractory disease (HR 0.52, 95% CI 0.33-0.83) and patients naive to autologous stem cell transplant (HR 0.61, 95% CI 0.42-0.89). Patients without prior exposure to brentuximab vedotin also had significantly improved PFS with pembrolizumab (HR 0.67, 95% CI 0.49-0.92).

"Pembrolizumab should be considered the preferred treatment option and new standard of care for the treatment of relapsed and refractory classical Hodgkin lymphoma in patients who relapsed after auto stem cell transplant or are ineligible for auto stem cell transplant," Zinzani said during a presentation for the media at the virtual meeting of the European Hematology Association.

Response rates were also improved with pembrolizumab compared to brentuximab vedotin (65.6% vs 54.2%, P=0.0225), driven by more partial responses (41.1% vs 30.1%). Median durations of response were 20.7 and 13.8 months, respectively.

Standard treatment for patients with relapsed or refractory classical Hodgkin's lymphoma has consisted of salvage chemotherapy and autologous stem cell transplantation, Zinzani explained, but no standard of care exists for those ineligible for transplant due to primary chemorefractory disease, age, or comorbidities.

was an open-label phase III trial that randomized 300 patients to 200-mg pembrolizumab or 1.8-mg/kg brentuximab vedotin, with both delivered intravenously every 3 weeks for up to 35 cycles. Median patient age was 36 and 35 years in the two arms, respectively. About 40% of patients in each arm had primary refractory disease, and 28% had relapsed within 12 months of their previous treatment.

Eligible patients had disease progression following prior autologous stem cell transplant (37%) or could not undergo transplant due to comorbidities, age, or other factors (63%). Patients were required to have good performance status (Eastern Cooperative Oncology Group 0-1). Prior brentuximab vedotin, while allowed in the study, was rare at 3.3% in the pembrolizumab arm and 6.5% in the brentuximab vedotin arm.

Grade 3 or higher adverse events (AEs) were similar between the two arms (43.9% with pembrolizumab and 43.4% with brentuximab vedotin). While serious AEs were increased with pembrolizumab (29.7% vs 21.1%), a slightly higher proportion stopped treatment for toxicity on the brentuximab vedotin arm (17.8% vs 13.5%).

Overall, nearly all patients experienced AEs regardless of treatment, and events were consistent with the known safety profiles of the two drugs, said Zinzani. Pembrolizumab was associated with higher rates of hypothyroidism (15.5% vs 1.3% with brentuximab vedotin), pyrexia (12.8% vs 5.9%), and pruritis (10.8% vs 5.3%). Brentuximab vedotin, on the other hand, was associated with more peripheral neuropathy (18.4% vs 2.0% with pembrolizumab), peripheral sensory neuropathy (13.2% vs 2.0%), nausea (13.2% vs 4.1%), and fatigue (10.5% vs 8.8%).

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