Treatment with the PD-1 inhibitor pembrolizumab (Keytruda) significantly extended progression-free survival (PFS) in patients with classical Hodgkin lymphoma compared with standard treatment with brentuximab vedotin (Adcetris), according to the results of the phase 3 KEYNOTE-204 clinical trial reported at the ASCO 2020 virtual annual meeting.
The median PFS was 4.9 months longer with pembrolizumab than with brentuximab vedotin (13.2 months vs 8.3 months, respectively; P = .00271), and the benefits of pembrolizumab were observed across key subgroups, including in patients eligible for autologous stem-cell transplant (ASCT), those with primary refractory disease, and patients who did not receive brentuximab vedotin previously.
“Based on these findings, pembrolizumab should be considered the preferred treatment option and new standard of care for relapsed or refractory classical Hodgkin lymphoma in patients who have relapsed post-ASCT or are ineligible for ASCT,” said lead investigator John Kuruvilla, MD, FRCPC, Clinician Investigator, Princess Margaret Cancer Centre, Toronto, Canada.
The current standard of care for relapsed or refractory classical Hodgkin lymphoma is salvage chemotherapy and ASCT. There is currently no standard-of-care treatment for patients who are ineligible for ASCT because of chemotherapy-refractory disease, age, or comorbidities.
The KEYNOTE-204 study randomized 304 patients (aged ≥18 years) in a 1:1 ratio to pembrolizumab 200 mg every 3 weeks or to intravenous brentuximab vedotin 1.8 mg/kg every 3 weeks. The patients had received ASCT or were ineligible for ASCT and were eligible for participation in the study regardless of previous use of brentuximab vedotin.
All patients had Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 and measurable disease, defined as having ≥1 lesions that could be measured in at least 2 dimensions by computed tomography (CT) or CT and positron emission tomography imaging. The patients were stratified according to whether they had ASCT and according to status after first-line therapy (ie, primary refractory, relapse <12 months after end of first-line therapy or ≥12 months later).
At baseline, the patients’ median age was approximately 35 years. In the pembrolizumab and brentuximab vedotin arms, respectively, 57% and 65.3% of the patients had an ECOG performance score of 0. A total of 3.3% and 6.5% of patients in the pembrolizumab and brentuximab vedotin arms, respectively, had previously received brentuximab vedotin.
The median follow-up was 24.7 months, and the median time spent receiving therapy was 305 days for pembrolizumab and 146.5 days for brentuximab vedotin.
In the primary analysis, pembrolizumab significantly improved PFS over brentuximab vedotin, which reduced the risk for progression or death by 35% (P = .00271). The 12-month PFS rate was 53.9% in the pembrolizumab group versus 35.6% in the brentuximab vedotin group.
Treatment with pembrolizumab reduced the risk for disease progression or death by 39% in patients with no ASCT, by 48% in patients with primary refractory disease, by 66% in patients with previous brentuximab vedotin, and by 33% in brentuximab vedotin treatment–naïve patients compared with treatment with brentuximab vedotin.
The objective response rate was 65.6% with pembrolizumab and 54.2% with brentuximab vedotin. The median duration of response was longer with pembrolizumab than with brentuximab vedotin (20.7 months vs 13.8 months, respectively).
Grade 3 to 5 treatment-related adverse events were reported in 19.6% of the pembrolizumab group versus in 25% of the brentuximab vedotin group. There was 1 death in the pembrolizumab group from grade 5 pneumonia.
Immune-mediated adverse events were higher in the pembrolizumab arm than in the arm that received brentuximab vedotin; the most common of these events were hypothyroidism (18.9%) and pneumonitis (10.8%). Of the 16 patients with pneumonitis, 15 required corticosteroids and 12 cases resolved.