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).

Abstract

8005 Background: PD-1 blockade via pembro monotherapy showed antitumor activity in R/R cHL. KEYNOTE-204 (NCT02684292) was a randomized, international, open-label, phase III study of pembro vs BV in R/R cHL. Methods: Patients (pts) were aged ≥18 y, were post−autologous stem cell transplant (auto-SCT) or ineligible for auto-SCT, and had measurable disease and ECOG PS 0 or 1. BV-naive and BV-exposed pts were eligible. Pts were randomized 1:1 to pembro 200 mg IV Q3W or BV 1.8 mg/kg IV Q3W and stratified by prior auto-SCT (yes vs no) and status after 1L therapy (primary refractory vs relapsed <12 mo vs relapsed ≥12 mo after end of 1L therapy). Primary end points: PFS by blinded independent central review (BICR) per International Working Group (IWG) criteria including clinical and imaging data after auto-SCT or allogeneic SCT (allo-SCT) and OS. Key secondary end points: PFS excluding clinical and imaging data after auto-SCT or allo-SCT (PFS-secondary), and ORR by BICR per IWG, PFS by investigator review per IWG, and safety. Exploratory end point: DOR by BICR per IWG. Results: 304 pts were randomized and 300 were treated (148, pembro; 152, BV); 256 discontinued. Median (range) follow-up: 24.7 (0.6-42.3) mo. 15 pts were BV exposed. Median (range) time on treatment was 305.0 (1-814) and 146.5 (1-794) days with pembro and BV, respectively. Statistically significant improvement was observed with pembro vs BV for primary PFS analysis (HR 0.65 [95% CI 0.48-0.88; P =0.00271]; median 13.2 vs 8.3 mo); 12-mo PFS rates were 53.9% vs 35.6%, respectively. Benefit was observed in all subgroups tested, including pts with no auto-SCT (HR=0.61), primary refractory disease (HR=0.52), prior BV (HR=0.34) and BV naive (HR=0.67). Significant improvement in PFS-secondary was observed with pembro vs BV (HR 0.62 [95% CI 0.46-0.85]; median 12.6 vs 8.2 mo). Per investigator assessment, PFS was longer with pembro vs BV (HR 0.49 [95% CI 0.36-0.67]; median 19.2 vs 8.2 mo). ORR was 65.6% for pembro and 54.2% for BV; CR rates were 24.5% and 24.2%, respectively. Median (range) DOR was 20.7 mo (0.0+ to 33.2+) for pembro and 13.8 mo (0.0+ to 33.9+) for BV. Grade 3-5 TRAEs: 19.6% of pts with pembro and 25.0% with BV. One death due to TRAE occurred with pembro (pneumonia). Conclusions: In pts with R/R cHL, pembro was superior to BV and demonstrated statistically significant and clinically meaningful improvement in PFS across all subgroups, with safety consistent with previous reports. Pembro monotherapy should be standard of care for this pt population with R/R/cHL. Clinical trial information: NCT02684292 .

Hodgkin Lymphoma—Review on Pathogenesis, Diagnosis, Current and Future Treatment Approaches for Adult Patients

“…For the overall group, there was a statistically significant better PFS for pembrolizumab of 13.2 vs. 8.3 months. Although the results of the study have not yet been available as a full text publication and Pembrolizumab is not yet approved by the EMA for this indication, the results seem so convincing that Pembrolizumab should be discussed as a new standard for patients with relapse after autologous SCT [ 78 ].…”

Hodgkin lymphoma. ASCO, EHA and ASH 2020 news

“…Существующие возможности для лечения этой категории пациентов весьма ограничены и недостаточно эффективны. В мае 2020 г. на Ежегодном собрании Американского общества клинической онкологии 2020 (American Society of Clinical Oncology Annual Meeting -ASCO) и в декабре 2020 г. на 62-й конференции ASH представлены результаты протокола KEYNOTE-204 по сравнению эффективности пембролизумаба (151 пациент) в монорежиме и брентуксимаба ведотина (153 пациента) в монорежиме у больных с р/р кЛХ [16][17][18]. В исследование включены больные с рецидивом после ВДХТ с аутоТСКК и больные с р/р кЛХ после 1-й линии терапии -не кандидаты на ВДХТ.…”

“…12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 52 54 56 58 60 62 64 66 68 70 72 74 76 78 80 82 84 86…”

Therapeutic Updates for Relapsed and Refractory Classical Hodgkin Lymphoma

“…Complete responses were observed in 24% of each group. The median PFS was 12.6 months with pembrolizumab and 8.2 months with BV and the median duration of response was 21 months with pembrolizumab and 14 months with BV [ 48 ]. This study supported the superiority of pembrolizumab (anti-PD-1 therapy) over BV in r/r cHL; however, there are still few long-term, relapse-free survivors in either treatment group, so most patients will eventually be treated with both agents at some time in the course of therapy for r/r cHL.…”