Treatment with the anti–PD-1 antibody pembrolizumab significantly extended progression-free survival (PFS) in patients with classic Hodgkin lymphoma (HL) compared with standard brentuximab vedotin (BV) therapy in the phase 3 KEYNOTE-204 trial reported at the ASCO20 Virtual Scientific Program.
Median PFS was 4.9 months longer with pembrolizumab (13.2 months vs 8.3 months with BV; P = .00271), and the benefits of pembrolizumab were observed across key subgroups, including patients eligible for autologous stem cell transplant (ASCT), patients with primary refractory disease, and patients who were BV-naive.
“Based on these findings, pembrolizumab should be considered the preferred treatment option and new standard of care for relapsed/refractory classic HL in patients who have relapsed post-ASCT or are ineligible for ASCT,” said lead author John Kuruvilla, MD, Princess Margaret Cancer Centre, Toronto, Canada.
The current standard of care for relapsed/refractory classic HL is salvage chemotherapy and ASCT. Right now, there is no standard of care for patients who are ineligible for ASCT due to chemotherapy-refractory disease, age, or comorbidities.
KEYNOTE-204 randomized 304 patients 1:1 to pembrolizumab 200 mg every 3 weeks or intravenous BV 1.8 mg/kg every 3 weeks. Patients were aged 18 or older and were either post-ASCT or ASCT ineligible. Both BV-naive and BV-treated patients were eligible for the trial.
All patients had ECOG performance status 0-1 and measurable disease (defined as at least 1 lesion that could be measured in at least 2 dimensions by CT or CT/PET imaging). Patients were stratified according to prior ASCT or no prior ASCT. They were also stratified according to status after first-line therapy (ie, primary refractory, relapsed <12 months after end of first-line therapy, or relapsed ≥12 months later).
At baseline, median age was about 35 years. In the pembrolizumab and BV arms, respectively, 57% and 65.3% had ECOG performance score 0. Prior exposure to BV was found in 3.3% and 6.5%, respectively.
Median follow-up was 24.7 months. Median time spent on therapy was 305 days for pembrolizumab and 146.5 days on BV.
In the primary analysis, pembrolizumab significantly improved PFS over BV, reducing the risk of progression or death by 35% (P = .00271). Twelve-month PFS rate was 53.9% in the pembrolizumab group versus 35.6% in the BV group.
Pembrolizumab reduced the risk of progression or death by 39% in patients with no ASCT; by 48% in patients with primary refractory disease; by 66% in patients with prior BV; and by 33% in BV-naive patients compared with BV.
The objective response rate was 65.6% for pembrolizumab and 54.2% for BV. Median duration of response was longer with pembrolizumab: 20.7 months versus 13.8 months.
Grade 3 to 5 treatment-related adverse events were reported in 19.6% of the pembrolizumab group versus 25% of the BV group. There was 1 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%). Fifteen of 16 patients with pneumonitis required corticosteroids, and 12 cases resolved.
The study was supported by Merck.