Micrograph showing HL
The anti-PD-1 therapy pembrolizumab could change the treatment paradigm of relapsed or refractory classic Hodgkin lymphoma (cHL), according to researchers.
In a phase 2 trial, pembrolizumab produced an overall response rate (ORR) of 69% and a complete response (CR) rate of 22% in adults with cHL who had failed treatment with brentuximab vedotin (BV), autologous hematopoietic stem cell transplant (auto-HSCT), or both.
The researchers said the safety profile of pembrolizumab was “acceptable” and largely consistent with safety in previous studies of the drug.
Twelve percent of patients temporarily stopped taking pembrolizumab due to treatment-related adverse events (AEs), and 4% stopped taking the drug entirely as a result of AEs.
Craig H. Moskowitz, MD, of Memorial Sloan Kettering Cancer Center in New York, New York, and his colleagues reported these results, from the KEYNOTE-087 trial, in the Journal of Clinical Oncology.
The trial was sponsored by Merck, the company that markets pembrolizumab as Keytruda.
In KEYNOTE-087, the researchers evaluated pembrolizumab (a 200 mg fixed dose every 3 weeks) in patients with relapsed or refractory cHL across 3 cohorts:
Cohort 1: Patients who progressed after auto-HSCT and subsequent treatment with BV
Cohort 2: Patients who failed salvage chemotherapy, were ineligible for a transplant, and progressed after BV
Cohort 3: Patients who progressed after auto-HSCT and did not receive BV after transplant.
Efficacy
Across all 210 enrolled patients, the ORR was 69.0%, and the CR rate was 22.4%.
In Cohort 1 (n=69), the ORR was 73.9%. The CR rate was 21.7%, the partial response (PR) rate was 52.2%, 15.9% of patients had stable disease (SD), and 7.2% progressed. In 82.2% of responders, the response lasted 6 months or more.
In Cohort 2 (n=81), the ORR was 64.2%. The CR rate was 24.7%, the PR rate was 39.5%, 12.3% of patients had SD, and 21.0% progressed. In 70.0% of responders, the response lasted 6 months or more.
In Cohort 3 (n=60), the ORR was 70.0%. Twenty percent of patients had a CR, 50.0% had a PR, 16.7% had SD, and 13.3% progressed. In 75.6% of responders, the response lasted 6 months or more.
Results also included an analysis of patients with primary refractory disease (n=73), which was defined as failure to achieve CR or PR with first-line treatment. In this patient population, the ORR was 79.5%.
An ORR of 67.8% was reported in patients who relapsed after 3 or more lines of prior therapy (99/146).
For the entire study cohort, the median duration of response was not reached, and the median overall survival was not reached. At 9 months, the overall survival rate was 97.5%, and the progression-free survival rate was 63.4%.
Safety
The most common AEs related to pembrolizumab were hypothyroidism (12.4%), pyrexia (10.5%), fatigue (9.0%), rash (7.6%), diarrhea (7.1%), headache (6.2%), nausea (5.7%), cough (5.7%), and neutropenia (5.2%).
The most common grade 3/4 treatment-related AEs were neutropenia (2.4%), diarrhea (1.0%), and dyspnea (1.0%). Immune-mediated AEs included pneumonitis (2.9%), hyperthyroidism (2.9%), colitis (1.0%), and myositis (1.0%).
Nine patients (4.3%) stopped taking pembrolizumab due to treatment-related AEs, including myocarditis, myelitis, myositis, pneumonitis, infusion-related reactions, and cytokine release syndrome.
Twenty-six patients (12.4%) had treatment interruptions due to pembrolizumab-related AEs.
Two patients died during follow-up, but neither death was considered related to pembrolizumab. One patient died of septic shock and the other of acute graft-versus-host disease.
