Treatment with anti-PD-1 antibody pembrolizumab prolonged progression-free survival (PFS) more than brentuximab vedotin (BV) in patients with relapsed or refractory classic Hodgkin lymphoma (R/R cHL), including patients ineligible for transplant, according to findings from the phase III KEYNOTE-204 trial (NCT02684292) presented as part of the ASCO20 Virtual Scientific Program.
Salvage chemotherapy and autologous hematopoietic cell transplant (AHCT) represent the standard of care for R/R cHL, explained study author John Kuruvilla, MD, of the Princess Margaret Cancer Centre in Toronto, ON, Canada. Unfortunately, there is no standard of care for patients who are ineligible for AHCT due to chemotherapy-refractory disease, comorbidities, or advanced age. Based on the findings from KEYNOTE-204, Dr. Kuruvilla said, “Pembrolizumab should be considered the preferred treatment option and new standard of care for the treatment of R/R cHL in patients that have relapsed post AHCT or are ineligible for AHCT.”
The trial enrolled patients with R/R cHL who had either undergone, or were ineligible for, AHCT. Patients were eligible regardless of prior exposure to BV. All patients had an Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1 and measurable disease. Measurable disease was defined as ≥1 lesion that could be measured in ≥2 dimensions with the use of a spiral computed tomography (CT) scan or combined CT plus positron emission tomography (PET) scan.
Patients were randomly assigned to either intravenous pembrolizumab 200 mg every 3 weeks (n=148) or intravenous BV 1.8 mg/kg every 3 weeks (n=152). The investigators stratified patients within treatment groups by whether they had a prior AHCT (pembrolizumab: n=56; BV: n=56) or had no history of AHCT (pembrolizumab: n=95; BV: n=97).
Additionally, patients were stratified by post-first line (1L) therapy status:
- primary refractory after end of 1L (pembrolizumab: n=61; BV: n=62)
- relapsed <12 months after end of 1L (pembrolizumab: n=42; BV: n=42)
- relapsed ≥12 months after end of 1L (pembrolizumab: n=48; BV: n=49)
The primary endpoints of the trial included PFS and overall survival (OS). Secondary endpoints included the objective response rate (ORR) and safety as well as duration of response (DOR).
In the pembrolizumab and BV groups, the median ages were 36 years (range = 18-84) and 35 years (range = 18-83), respectively. More than half of patients had an ECOG score of 0 in the pembrolizumab (57%) and BV (65.3%) arms. Only 3.3% of patients randomized to pembrolizumab and 6.5% of patients randomized to BV had prior exposure to BV.
Prior radiation was recorded for 38.4% of patients in the pembrolizumab group and 39.9% of patients in the BV group. The median number of prior therapies was 2 (range = 1-10) in the pembrolizumab arm and 3 (range = 1-11) in the BV group.
The median time from randomization to data cutoff was 25.7 months (range = 18.2-42.3), and the median follow-up period was 24.7 months (range = 0.6-42.3). The median time patients spent on therapy was 305 days (range = 1-814) for those receiving pembrolizumab and 146.5 days (range = 1-794) for those on BV.
A slightly smaller proportion of patients treated with pembrolizumab experienced grade 3 to 5 treatment-related adverse events (TRAEs) compared with BV (19.6% vs. 25.0%). There was 1 death associated with a TRAE, grade 5 pneumonia, recorded in the pembrolizumab arm.
In the primary PFS analysis, pembrolizumab was associated with significantly greater improvement in median PFS compared with pembrolizumab (13.2 vs. 8.3 months, respectively; hazard ratio [HR] = 0.65; 95% CI 0.48-0.88; p=0.00271). The 12-month PFS rate was 53.9% in the pembrolizumab group versus 35.6% in the BV group.
Treatment with pembrolizumab was also associated with significantly greater improvements in PFS compared with BV in various subgroups, including:
- patients with no AHCT (HR=0.61; 95% CI 0.42-0.89)
- patients with primary refractory disease (HR=0.52; 95% CI 0.33-0.83)
- patients with prior BV (HR=0.34; 95% CI 0.04-3.10)
- BV-naïve patients (HR=0.67; 95% CI 0.49-0.92)
The ORRs were 65.6% for pembrolizumab and 54.2% for BV. The complete response rates were 24.5% for pembrolizumab and 24.2% for BV. A longer median DOR was observed for pembrolizumab (20.7 months [range = 0.0+-33.2+]) versus BV (13.8 months [range=0.0+-33.9+]).
Study authors report relationships with Merck, which sponsored this trial.
Kuruvilla J, Ramchandren R, Santoro A, et al. KEYNOTE-204: Randomized, open-label, phase III study of pembrolizumab (pembro) versus brentuximab vedotin (BV) in relapsed or refractory classic Hodgkin lymphoma (R/R cHL). J Clin Oncol 38: 2020 (suppl; abstr 8005). Presented as part of the ASCO20 Virtual Scientific Program. May 29-31, 2020.