FDA Approves Pembrolizumab in Relapsed/Refractory Classical Hodgkin Lymphoma

The FDA granted approval to the immune checkpoint inhibitor pembrolizumab as treatment of patients with relapsed or refractory classic Hodgkin lymphoma.

The FDA has granted approval to the immune checkpoint inhibitor pembrolizumab (Keytruda) as treatment of patients with relapsed or refractory classic Hodgkin lymphoma (cHL), according to a press release from the drug developer, Merck.1

The approval was supported by findings from the pivotal phase 3 KEYNOTE-204 clinical trial, which demonstrated a significant improvement in progression-free survival (PFS) in patients with cHL receiving pembrolizumab compared with those who received the standard-of-care (SOC) therapy brentuximab vedotin (Adcetris).

“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,” said . John Kuruvilla, MD, hematologist and associate professor of medicine, Princess Margaret Cancer Centre and University of Toronto. “With this approval, Keytruda has the potential to change the current standard of care and help these patients achieve better outcomes.”

Results from KEYNOTE-204 presented during the American Society of Oncology (ASCO) Virtual Annual Meeting showed a 4.9-month PFS benefit with pembrolizumab when compared with SOC in patients with relapsed/refractory cHL. Pembrolizumab reduced the risk of disease progression by 35% compared with brentuximab vedotin, Specifically, the median PFS with pembrolizumab was 13.2 months versus 8.3 months with brentuximab vedotin (HR, 0.65; 95% CI, 0.48-0.88; P =.00271).2

Across multiple subgroup populations explored in the study, pembrolizumab was also favorable compared with SOC. Favorability specific showed in subgroup of patients who were ineligible for autologous stem cell transplant (HR, 0.52; 95% CI, 0.33-0.83), and those who had not received prior brentuximab vedotin (HR, 0.67; 95% CI, 0.49-0.92).

In terms of responses, the overall response rate observed with pembrolizumab was 65.6%, which included a 24.5% complete response rate and a 41.1% partial response rate. In comparison, the SOC arm had an ORR of 54.2%. The median duration of response observed in the pembrolizumab arm was 20.7 months versus 13.8 months in the control arm, demonstrating a 6.9-month increase over the standard of care.

The safety analysis showed no new safety signals with either drug administered in the study. There were serious treatment-related adverse events (TRAEs) observed, which occurred mainly in patients who received pembrolizumab. Overall, 16.2% of patients reported a serious TRAE. The most common TRAEs observed in the study were hypothyroidism (15.5%), pyrexia (12.8%), pruritis (10.8%), and fatigue (8.8%).

TRAEs led to treatment discontinuation in 19 patients (12.8%) in the pembrolizumab arm and 25 (16.4%) in the brentuximab vedotin arm. One patient in the pembrolizumab arm died as a result of grade 5 pneumonia.

Immune-mediated adverse events (IRAEs) were also revealed in the safety analysis and had a higher prevalence in the pembrolizumab arm compared with the control arm. The most common IRAEs observed included hypothyroidism (18.9%) and pneumonitis (10.8%). Notably, only 5.4% of cases of pneumonitis were grade 3/4 in severity, and 15 of the 16 pneumonitis cases were treated with corticosteroids, which was resolved in 12 patients.

KEYNOTE-204 was a randomized, open-label trial of 151 patients who were assigned to the pembrolizumab group and 153 to the control group. Patients in the study were stratified by whether or not they had undergone homologous stem cell transplant, and their disease status following front-line therapy.

To be enrolled, patients were required least 18 years of age to participate in the clinical trial and be either post autologous stem cell transplant or ineligible for transplant. Patients who had not received prior brentuximab vedotin and those who had been exposed to this agent were included in the study.

In addition to its success in the cHL population, KEYNOTE-204 was a confirmatory study that led to the accelerated approval of pembrolizumab in hematologic indications. 


1. FDA Approves Expanded Indication for Merck’s KEYTRUDA® (pembrolizumab) in Adult Patients With Relapsed or Refractory Classical Hodgkin Lymphoma (cHL). News release. Merck. October 15, 2020. Accessed October 15, 2020. https://bit.ly/3192L8C 

2. 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). doi: 10.1200/JCO.2020.38.15_suppl.8005