EC approval of pembrolizumab for adult and pediatric patients with R/R cHL

On March 18, 2021, it was announced that the European Commission (EC) approved pembrolizumab, an anti-PD-1 monoclonal antibody, for the treatment of adult and pediatric patients (≥3 years of age) with relapsed or refractory (R/R) classical Hodgkin lymphoma (cHL). This approval is for patients who have failed autologous hematopoietic stem cell transplant (auto-HSCT) or failed ≥2 prior therapies when auto-HSCT is not a treatment option.¹

This approval was based on data from the interim analysis of the phase III KEYNOTE-204 trial (NCT02684292) previously discussed by John Kuruvilla at the 2020 American Society of Clinical Oncology (ASCO) Annual Meeting. These results have recently been published in The Lancet Oncology and are summarized below.² The EC approval was also based on supportive data from an updated analysis of the phase II KEYNOTE‑087 trial (NCT02453594), previously reported on the Lymphoma Hub.    

KEYNOTE-204 trial (NCT02684292)^1–3

• An ongoing multicenter, randomized, open-label, phase III study investigating the use of pembrolizumab compared with brentuximab vedotin (BV) in adult patients with R/R cHL
• Data cut for interim analysis: January 16, 2020
• Estimated study completion date: July 18, 2025
• Randomization: 1:1 (pembrolizumab, n = 151; BV, n = 153)
• Dosage: Pembrolizumab 200 mg intravenously every 3 weeks or BV 1.8 mg/kg intravenously every 3 weeks
• Primary outcomes: Progression-free survival and overall survival
• Secondary outcome measure: Overall response rate

Interim results^1,2

• Pembrolizumab significantly reduced the risk of disease progression or death by 35% (hazard ratio, 0.65; 95% CI, 0.48–0.88; p = 0.0027), with a median progression-free survival of 13.2 months (95% CI, 10.9–19.4) compared with 8.3 months (95% CI, 5.7–8.8) for patients treated with BV.
• Although the overall response rate was higher with pembrolizumab compared with BV (66% vs 54%), this difference was not statistically significant (Table 1).

Table 1. Response in the pembrolizumab cohort vs BV cohort*

BV, brentuximab vedotin; CR, complete response; mDOR, median duration of response, ORR, overall response rate; PD, progressive disease; PR, partial response; SD, stable disease. *Data from Kuruvilla et al.1 †Assessed by blinded independent central review by the International Working Group 2007 criteria.
Response†	Pembrolizumab (n = 151)	BV (n = 153)
ORR, %	66	54
CR	25	24
PR	41	30
SD, %	14	24
PD, %	17	18
mDOR, months (95% CI)	20.7 (12.4–not reached)	13.8 (5.8–not reached)

• The safety results were consistent with the established safety profile for each agent and adverse events were manageable with standard clinical practice. Adverse events were generally less frequent for the pembrolizumab cohort.
  • The most common Grade 3–5 treatment-related adverse events were pneumonitis (4% in the pembrolizumab cohort vs 1% in the BV cohort), neutropenia (2% vs 7%, respectively), decreased neutrophil count (1% vs 5%, respectively), and peripheral neuropathy (1% vs 3%, respectively).
• Serious treatment-related adverse events occurred in 16% of patients receiving pembrolizumab vs 11% for those receiving BV. One treatment-related death due to pneumonia occurred in the pembrolizumab cohort.
• Adverse event-related discontinuation occurred less frequently in the pembrolizumab arm compared with the BV arm (13% vs 16%).