Treatment with the anti–PD-1 agent pembrolizumab significantly improved progression-free survival in patients with classical Hodgkin lymphoma compared with standard brentuximab vedotin, according to results of the phase III KEYNOTE-204.1 The study results were presented during the ASCO20 Virtual Scientific Program by John Kuruvilla, MD. Dr. Kuruvilla, lead author of the study, is a Clinician Investigator in the Cancer Clinical Research Unit at Princess Margaret Cancer Centre, in Toronto.
John Kuruvilla, MD
For patients with classical Hodgkin lymphoma who relapse, treatment is with salvage chemotherapy and autologous stem cell transplant (ASCT). But prior to this study, there was no good option for patients who are ineligible for ASCT due to chemotherapy-refractory disease, age, or comorbidities.
KEYNOTE-204 randomized 304 patients 1:1 to pembrolizumab at a dose of 200 mg intravenously on day 1 of every 3-week cycle vs intravenous brentuximab vedotin at 1.8 mg/kg on day 1 of each 3-week cycle for up to 35 cycles. Patients were aged 18 or older and were either post-ASCT or ASCT-ineligible. Both brentuximab-naive and brentuximab-treated patients were eligible for the trial.
Median follow-up was 24.7 months. In the primary analysis, pembrolizumab significantly improved disease progression-free survival over brentuximab vedotin, reducing the risk of progression or death by 35% (P = .00271). The 12-month progression-free survival rate was 53.9% in the pembrolizumab group vs 35.6% in the brentuximab group.
Median progression-free survival was 13.2 months vs 8.3 months with brentuximab vedotin (P = .00271), an absolute difference of 4.9 months favoring pembrolizumab. Pembrolizumab’s benefit on progression-free survival was seen in all key subgroups: eligible for ASCT, primary refractory disease, and brentuximab-naïve.
“Based on these findings, pembrolizumab should be considered the preferred treatment option and new standard of care for relapsed/refractory classical Hodgkin in patients who have relapsed post-ASCT or are ineligible for ASCT,” said Dr. Kuruvilla.
Efficacy and Safety
Compared to brentuximab vedotin, pembrolizumab reduced the risk of disease progression or death by 39% in patients with no ASCT; by 48% in patients with primary refractory disease; by 66% in patients with prior brentuximab; and by 33% in brentuximab-naive patients.
Objective response rate was 65.6% for pembrolizumab and 54.2% for brentuximab. Median duration of response was longer with pembrolizumab: 20.7 months vs 13.8 months.
Grade 3 to 5 treatment-related adverse events were reported in 19.6% of the pembrolizumab group vs 25% of the brentuximab group. There was one death in the pembrolizumab group due to grade 5 pneumonia.Immune-mediated adverse events were higher in the pembrolizumab arm; the most common of these events were hypothyroidism (18.9%) and pneumonitis (10.8%). Of 16 patients, 15 with pneumonitis required corticosteroids and 12 cases resolved.
Disclosure: KEYNOTE-204 was supported by Merck. Dr. Kuruvilla has received honoraria from, or consulted/advised for, AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Celgene, Gilead, Janssen, Karyopharm Therapeutics, Merck, Novartis, Pfizer, Roche, and Seattle Genetics, and has received research funding from Celgene, Janssen, and Roche.
1. Kuruvilla J, Ramchandren R, Santoro A, et al. KEYNOTE-204. ASCO20 Virtual Scientific Program. Abstract 8005.