FDA Approves Expanded Indication of Pembrolizumab for Relapsed/Refractory cHL

The FDA approved an expanded label for pembrolizumab (Keytruda) as monotherapy for the treatment of adult patients with relapsed or refractory classical Hodgkin lymphoma.

The FDA has approved an expanded label for the anti-PD-1 therapy pembrolizumab (Keytruda) for the monotherapy treatment of adult patients with relapsed or refractory classical Hodgkin lymphoma (cHL), according to Merck, the developer of the agent.

In addition, the FDA also approved an updated pediatric indication for pembrolizumab for the treatment of pediatric patients with refractory cHL, or cHL that has relapsed after 2 or more lines of therapy.

The approval was reviewed under the FDA’s Project Orbis. For this application, a modified Project Orbis was initiated, and the FDA is collaborating with the Australian Therapeutic Goods Administration and Health Canada on their ongoing review of the application.

“The patients with cHL who do not achieve remission following initial treatment or who relapse after transplantation face a poor prognosis, reflecting the unmet need for improved therapies in the relapsed/refractory setting,” John Kuruvilla, MD, hematologist and associate professor of medicine at Princess Margaret Cancer Centre and University of Toronto, said in a press release. “With this approval, [pembrolizumab] has the potential to change the current standard of care and help these patients achieve better outcomes.”

The approval was based on results from the randomized, open-label, active-controlled, phase 3 KEYNOTE-204 trial. The trial enrolled 304 adults with relapsed or refractory disease after at least one multi-agent chemotherapy regimen. Participants were randomized 1:1 to receive either 200 mg of pembrolizumab intravenously every 3 weeks (n = 151) or 1.8 mg/kg of brentuximab vedotin, or BV (Adcetris; n = 153), intravenously every 3 weeks.

Treatment was continued until unacceptable toxicity, documented disease progression, or a maximum of 35 cycles (up to approximately 2 years); disease assessment was performed every 12 weeks. The primary end point for the study was progression-free survival (PFS) as assessed by blinded independent central review (BICR) using 2007 revised International Working Group (IWG) criteria.

The median number of prior therapies was 2 (range, 1-10) in the pembrolizumab arm and 3 (range, 1-11) in the BV arm, with 18% in both arms having received 1 prior line. Moreover, 42% of patients were refractory to the last prior therapy, 29% had primary refractory disease, 37% had prior autologous HSCT, 5% had received prior BV, and 39% had prior radiation therapy.

In the study, pembrolizumab reduced the risk of disease progression or death by 35% (HR, 0.65; 95% CI, 0.48-0.88; P = .0027) and demonstrated a median PFS of 13.2 months (95% CI, 10.9-19.4). For patients treated with BV, median PFS was 8.3 months (95% CI, 5.7-8.8). Specifically, there were 81 patients (54%) with an event in the pembrolizumab arm versus 88 patients (58%) in the BV arm.

For those treated with pembrolizumab, the objective response rate (ORR) was 66% (95% CI, 57-73), with a complete response (CR) rate of 25% and a partial response (PR) rate of 41%. For patients treated with BV, the ORR was 54% (95% CI, 46-62), with a CR rate of 24% and a PR rate of 30%. However, the difference in ORRs was not statistically significant.

Among the responding patients, median duration of response (DOR) was 20.7 months (range, 0.0+ to 33.2+) with pembrolizumab and 13.8 months (range, 0.0+ to 33.9+) with BV. The median duration of exposure to pembrolizumab was 10 months (range, 1 day to 2.2 years), with 68% receiving at least 6 months of treatment and 48% receiving at least 1 year of treatment.

Serious adverse events (AEs) were observed in 30% of patients who received pembrolizumab. Serious AEs in those greater than or equal to 1% of patients included pneumonitis, pneumonia, pyrexia, myocarditis, acute kidney injury, febrile neutropenia, and sepsis. Additionally, 3 patients (2%) died from causes other than disease progression, including 2 from complications after allogeneic hematopoietic stem cell transplantation (HSCT) and 1 from an unknown cause.

Further, 14% of patients permanently discontinued pembrolizumab due to an AE, with 7% of patients discontinuing due to pneumonitis. Dosage interruption of pembrolizumab due to an AE also occurred in 30% of patients. AEs that required dosage interruption in greater than or equal to 3% of patients were upper respiratory tract infection, pneumonitis, transaminase increase, and pneumonia. Thirty-eight percent of patients also had an AE requiring systemic corticosteroid therapy.

The most common AEs greater than or equal to 20% were upper respiratory tract infection (41%), musculoskeletal pain (32%), diarrhea (22%), and pyrexia, fatigue, rash and cough (20% each).

Pembrolizumab was previously approved by the FDA under accelerated approval for the treatment of adult and pediatric patients with refractory cHL, or who have relapsed after 3 or more prior lines of therapy based on data from the KEYNOTE-087 trial. However, continued approval for this indication was contingent upon verification and description of clinical benefit; these accelerated approval requirements have been satisfied with the data from KEYNOTE-204.


FDA Approves Expanded Indication for Merck’s KEYTRUDA® (pembrolizumab) in Adult Patients With Relapsed or Refractory Classical Hodgkin Lymphoma (cHL) [news release]. Kenilworth, NJ. Published October 15, 2020. Accessed October 15, 2020. https://www.merck.com/news/fda-approves-expanded-indication-for-mercks-keytruda-pembrolizumab-in-adult-patients-with-relapsed-or-refractory-classical-hodgkin-lymphoma-chl/

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