PembrolizumabThe FDA has now expanded the approved indications for pembrolizumab (KEYTRUDA®, Merck Sharp & Dohme) to include both adult patients with relapsed or refractory classical Hodgkin lymphoma (cHL) and pediatric patients with refractory cHL, or cHL that has relapsed after two or more lines of therapy.
The approval was based on efficacy data from the open-label phase 3 KEYNOTE-204 trial (NCT02684292), for which 304 adult patients with cHL previously treated with at least one multiagent regimen were randomized in a 1:1 ratio to receive either intravenous pembrolizumab 200 mg every three weeks or brentuximab vedotin 1.8 mg/kg every three weeks for up to two years. The study's primary efficacy end points were progression-free survival, as assessed by blinded independent central review, and overall survival. Of the 304 patients who were randomized, 300 were treated.
At a primary analysis of progression-free survival, completed with a median follow-up of 24.7 months, the median progression-free survival was longer with pembrolizumab compared with brentuximab vedotin (13.2 vs 8.3 months), with a higher 12-month progression-free survival rate for pembrolizumab (53.9% vs 35.6% for brentuximab vedotin). Pembrolizumab also resulted in a higher objective response rate (65.6% vs 54.2%) and a longer median duration of response (20.7 vs 13.8 months). Complete response rates were similar between the two regimens, at 24.5% for pembrolizumab and 24.2% for brentuximab vedotin.
Grade 3-5 treatment-related adverse events occurred in 19.6% of patients taking pembrolizumab, compared with 25.0% of patients taking brentuximab vedotin. One treatment-related death occurred from pneumonia in a patient in the pembrolizumab arm.
Adverse reactions affecting at least 20% of patients taking pembrolizumab included upper respiratory tract infection, musculoskeletal pain, diarrhea, cough, pyrexia, fatigue, and rash. Thirty-eight percent of patients had adverse reactions requiring systemic corticosteroids, and 11% had pneumonitis.
"In patients with relapsed/refractory cHL, pembrolizumab was superior to bevacizumab vedotin and demonstrated statistically significant and clinically meaningful improvement in progression-free survival across all subgroups, with safety consistent with previous reports," concluded the KEYNOTE-204 investigators in their presentation abstract at the 2020 American Society of Clinical Oncology (ASCO) Virtual Scientific Program, led by John Kuruvilla, MD, FRCPC, of the Princess Margaret Cancer Centre in Toronto, Ontario, Canada. "Pembrolizumab monotherapy should be standard of care for this patient population with relapsed/refractory cHL."
For patients with cHL, pembrolizumab dosages are 200 mg every three weeks or 400 mg every six weeks intravenously for adults, or 2 mg/kg (up to 200 mg) every three weeks intravenously for pediatric patients, for up to two years.
For More Information
Kuruvilla J, Ramchandren R, Santoro A, et al (2020). 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 (ASCO Virtual Scientific Program), 38 (suppl_15). DOI:10.1200/JCO.2020.38.15_suppl.8005.
Clinicaltrials.gov (2020). Study of pembrolizumab (MK-3475) vs. brentuximab vedotin in participants with relapsed or refractory classical Hodgkin lymphoma (MK-3475-204/KEYNOTE-204). NLM identifier: NCT02684292.
US Food & Drug Administration (2020). FDA extends approval of pembrolizumab for classical Hodgkin lymphoma. Available at: https://www.fda.gov/drugs/drug-approvals-and-databases/fda-extends-approval-pembrolizumab-classical-hodgkin-lymphoma#:~:text=On%20Oct
Image credit: Mark Ong. Licensed under CC BY-SA 4.0