Efficacy and Safety of Pembrolizumab Every Six Weeks in Relapsed/Refractory Classical Hodgkin Lymphoma or Primary Mediastinal B-Cell Lymphoma: Keynote-B68 Update

Background: Pembrolizumab 200mg Q3W is approved for treatment of relapsed/refractory (R/R) classical Hodgkin lymphoma (cHL) and R/R primary mediastinal B-cell lymphoma (PMBCL). The FDA granted accelerated approval to pembrolizumab 400 mg Q6W in all approved indications based on data in solid tumors. The global Phase 2 KEYNOTE-B68 trial (NCT04875195) evaluates the efficacy and safety of pembrolizumab 400 mg Q6W in patients with R/R cHL or R/R PMBCL. We previously reported an objective response rate (ORR) of 67% for patients with R/R cHL, and 50% for patients with R/R PMBCL with 16 months (mo) of follow up. Here we present data from 66 patients with an additional 12 mo of follow up.

Methods: In this nonrandomized, open-label trial, patients aged ≥18 years with PD-1 inhibitor naïve R/R cHL or PMBCL received 400 mg pembrolizumab Q6W for ≤ 18 cycles, until progression, unacceptable toxicity, or withdrawal. Eligible patients with cHL must have relapsed or failed to respond after ≥1 prior lines of therapy. Eligible patients with PMBCL must have relapsed or failed to respond after ≥2 prior lines of therapy including rituximab and relapsed or failed to respond to or were ineligible for auto-SCT. The primary endpoint was ORR per Lugano criteria by investigator. Secondary endpoints were DOR per Lugano criteria by investigator and safety. Exploratory endpoints were PFS per Lugano criteria by investigator and OS. Data cut-off date was May 13, 2024.

Results: At data cut-off, 66 patients (60 R/R cHL, 6 R/R PMBCL) were enrolled. Overall, 53 (80%) patients discontinued treatment, 39 (56%) due to progressive disease, 9 (14%) due to SCT, 2 (3%) due to adverse events (AE), 2 (3%) withdrawals and 1 (2%) due to physician decision. A total of 51 patients with R/R cHL and 6 with R/R PMBCL had ≥2 prior lines of therapy. The median follow-up was 27.7 mo (range, 19.8 -34.7) for patients with R/R cHL and 29.4 mo (range, 23.9 - 34.2) with R/R PMBCL. The ORR was 66.7% (95% CI, 53.3 -78.3 [35.0% CR; 31.7% PR]) for patients with R/R cHL, and 50% (95% CI, 11.8 -88.2 [33.3% CR; 16.7% PR]) for R/R PMBCL. The median DOR was 15.2 mo (range, 0.0+ -29.8+) for patients with R/R cHL and 9.7 mo (range, 2.6 -9.7) for R/R PMBCL. Median PFS was 8.3 mo (95% CI: 5.6-13.8) for patients with R/R cHL and 4.1 mo (95% CI: 0.1 -not reached [NR]) for R/R PMBCL. Median OS was NR (95% CI: NR -NR) for patients with R/R cHL and 24.8 mo (95% CI: 6.7 -NR) for R/R PMBCL. Overall, 22 patients with R/R cHL received transplant (either autologous or allogenic) after stopping trial treatment, 12 had CR and 2 were not-evaluable (NE) after auto-SCT, and 7 had CR and 1 was NE after allogenic stem cell transplant (allo-SCT). Overall, 4 patients with R/R PMBCL received transplant (either autologous or allogenic) after stopping trial treatment, 1 had CR, 1 had PR, and 1 had progressive disease after auto-SCT, and 1 had CR after allo-SCT. Treatment-related AEs occurred in 26 (43%) patients with R/R cHL and 2 (33%) with R/R PMBCL. Grade ≥3 treatment-related AEs occurred in 3 (5%) patients with R/R cHL and 1 (17%) with R/R PMBCL. No grade 5 treatment-related AE occurred. Immune-mediated AEs occurred in 14 (23%) patients with R/R cHL and 1 (17%) with R/R PMBCL. Grade ≥3 immune-mediated AE occurred in 2 (3%) patients with R/R cHL. No grade 5 immune-mediated AEs occurred in patients with R/R cHL and no grade ≥3 immune-mediated AEs occurred in patients with R/R PMBCL.

Conclusions: With a total of 28 months of follow-up, pembrolizumab Q6W demonstrated durable responses in patients with R/R cHL and PMBCL and consistent with our previous reports. Additionally, no new safety concerns occurred in either cHL or PMBCL patient populations. The KEYNOTE-B68 trial demonstrates that pembrolizumab 400 mg Q6W maintains antitumor activity in these patients and confirms its acceptability in heme indications.