Early Results Find Pembrolizumab Active in Classical Hodgkin Lymphoma After Brentuximab Vedotin Failure
Findings in a classical Hodgkin lymphoma cohort in the phase Ib KEYNOTE-013 trial, reported by Armand et al in the Journal of Clinical Oncology, indicate that pembrolizumab (Keytruda) is active in patients with disease progressing on or after brentuximab vedotin (Adcetris) treatment.
Study Details
The study included 31 patients with relapsed or refractory Hodgkin lymphoma progressing on or after brentuximab vedotin treatment. Patients received pembrolizumab at 10 mg/kg every 2 weeks until disease progression or unacceptable toxicity. Overall, 55% of patients had at least four lines of prior therapy, and 71% had relapsed after autologous stem cell transplantation.
Toxicity
The most common treatment-related adverse events of any grade were hypothyroidism (16%), diarrhea (16%), nausea (13%), and pneumonitis (10%). Grade 3 treatment-related adverse events occurred in five patients (16%) and consisted of colitis, increased alanine transaminase and aspartate transaminase, nephrotic syndrome, joint swelling, back pain, and axillary pain.
No grade 4 adverse events or treatment-related deaths were observed. Two patients discontinued treatment, due to grade 2 pneumonitis and grade 3 nephrotic syndrome.
Responses
Response occurred in 20 patients (65%), including complete remission in 5 (16%). Responses persisted for at least 24 weeks in 70% of responders. At a median follow-up of 17 months, response durations ranged from 0.14+ to 74+ weeks. Progression-free survival was 69% at 24 weeks and 46% at 52 weeks.
A high prevalence of PD-L1 (programmed cell death ligand 1) and PD-L2 (programmed cell death ligand 2) expression; treatment-induced expansion of T cells and natural killer cells; and activation of interferon-γ, T-cell receptor, and expanded immune-related signaling pathways were observed on biomarker analysis.
The investigators concluded: “Pembrolizumab was associated with a favorable safety profile. Pembrolizumab treatment induced favorable responses in a heavily pretreated patient cohort, justifying further studies.”
The study was funded by Merck.
Craig H. Moskowitz, MD, of Memorial Sloan Kettering Cancer Center, New York, is the corresponding author of the Journal of Clinical Oncology article.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
