Final Analysis of Keynote-170: Pembrolizumab in Relapsed or Refractory Primary Mediastinal Large B-Cell Lymphoma (PMBCL)
Authors: Zinzani Pier Luigi Luigi , Thieblemont Catherine , Melnichenko Vladimir , Bouabdallah Krimo , Waleswski Jan , Majlis Alejandro , Fogliatto Laura , Martin Garcia-Sancho Alejandro , Christian Beth , Gulbas Zafer , Özcan Muhit , Perini Guilherme Fleury , Salles Gilles , Shipp Margaret A. , Thompson Seth , Chakraborty Samhita , Marinello Patricia , Armand Philippe 
Published: November 2021

Introduction: Similar to classical Hodgkin lymphoma, primary mediastinal large B-cell lymphoma (PMBCL) expresses high level of the programmed cell death 1 (PD-1) ligands: PD-L1 and PD-L2. Prior analyses of the phase 2 KEYNOTE-170 (NCT02576990) study demonstrated that monotherapy with the PD-1 inhibitor pembrolizumab had effective antitumor activity and acceptable safety in relapsed/refractory (R/R) PMBCL, leading to FDA approval for adult patients with R/R PMBCL after ≥2 prior therapies. Long-term durability of response with PD-1 blockade in patients with PMBCL, especially those who achieve complete remission (CR), remains a critical clinical question. Here we present updated efficacy and safety of patients with R/R PMBCL in KEYNOTE-170 after ~4 years of follow-up.

Methods: Patients with R/R PMBCL who progressed after or were ineligible for autologous stem cell transplant and received ≥2 prior therapies received pembrolizumab 200 mg every 3 weeks (Q3W) for up to 35 cycles (~2 years). Response assessments were Q12W per 2007 Revised Response Criteria for Malignant Lymphomas. End points included overall response rate (ORR), progression-free survival (PFS), and duration of response (DOR) by investigator assessment; as well as overall survival (OS) and safety. Data cutoff date was October 23, 2020.

Results: At data cutoff, the median duration of follow-up was 48.7 months (range,41.2-56.2). Baseline characteristics of the patients have been previously described (Armand P, et al. J Clin Oncol. 2019; 37(34): 3291-3299). Among all treated patients (N=53), 13 completed 2 years of treatment and 40 patients discontinued, primarily due to progressive disease (n=18). ORR per investigator assessment was 41.5% (95% CI, 30.0-53.7), with 20.8% complete response rate and 20.8% partial response rate. Median DOR was not reached (NR) and 80.6% of patients had a response ≥48 months. Median PFS was 4.3 months (95% CI, 2.8-13.8) and the 48-month PFS rate was 33.0%. Median OS was 22.3 months (95% CI, 7.3-NR) and the 48-month OS rate was 45.3%. At data cutoff, treatment-related adverse events (AEs) of any grade occurred in 30 patients (56.6%); the most commonly reported (incidence &gt;5%) were neutropenia (18.9%), asthenia (9.4%), hypothyroidism (7.5%), and fatigue and pyrexia (5.7% each). Grade 3-4 treatment-related AEs occurred in 22.6% of patients; only neutropenia (n=7) occurred in ≥2 patients. No grade 5 treatment-related AEs occurred.

Conclusions: With 48.7 months of follow-up in heavily pretreated participants with R/R PMBCL, treatment with pembrolizumab monotherapy continued to demonstrate sustained antitumor activity. PFS and OS demonstrated promising trends for long-term survival with no new safety signals identified.

Disclosures

Zinzani: Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sandoz: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Verastem: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Merck Sharp & Dohme: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ImmuneDesign: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bristol Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ADC Therapeutics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Servier: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kyowa Kirin: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; EUSA Pharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BeiGene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen-Cilag: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; TG Therapeutics Inc: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celltrion: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Portola: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Thieblemont: Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Kyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb/Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses , Research Funding; Gilead Sciences: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Cellectis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Hospira: Research Funding; Bayer: Honoraria; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses . Bouabdallah: Sandoz: Consultancy, Honoraria; Kite/Gilead: Consultancy, Honoraria, Other: Travel/Accommodations/Expenses; Abbvie: Honoraria; Roche: Consultancy, Honoraria, Other: Travel/Accommodations/Expenses; Takeda: Consultancy, Honoraria, Other: Travel/Accommodations/Expenses. Waleswski: Roche: Consultancy, Honoraria, Other: Institution: Research Grant/Funding; Takeda: Consultancy, Honoraria; Servier: Honoraria; Gilead: Consultancy, Honoraria; Amgen: Honoraria; Novartis: Consultancy, Honoraria; GSK/Novartis: Other: Institution: Research Grant/Funding; Abbvie: Consultancy, Honoraria. Fogliatto: AstraZeneca: Speakers Bureau. Martin Garcia-Sancho: Celgene: Honoraria, Other: travel; Celgene/BMS: Consultancy; Janssen: Honoraria, Research Funding; Servier: Consultancy, Honoraria, Other: Travel/Accommodations/Expenses; Gilead: Consultancy, Honoraria; Morphosys: Consultancy; Kyowa Kirin: Consultancy; Clinigen: Consultancy; Eusa Pharma: Consultancy; Novartis: Consultancy; Takeda: Honoraria; Roche: Consultancy, Honoraria, Other: Travel/Accommodations/Expenses; Incyte: Consultancy; Kern Pharma: Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company). Christian: Celgene/BMS: Other: Institution: Research Grant/Funding; Acerta: Other: Institution: Research Grant/Funding; Seattle Genetics: Consultancy, Other: Institution: Research Grant/Funding; Genentech: Consultancy, Other: Institution: Research Grant/Funding; AstraZeneca: Consultancy; VeraStem: Consultancy; Morphosys: Consultancy, Other: Institution: Research Grant/Funding; Triphase: Other: Institution: Research Grant/Funding; Millenium: Other: Institution: Research Grant/Funding; Immunomedics: Other: Institution: Research Grant/Funding; Merck: Other: Institution: Research Grant/Funding. Özcan: Amgen: Honoraria, Other: Travel/Accommodations/Expenses; Janssen: Other: Travel/Accommodations/Expenses, Research Funding; Celgene: Research Funding; Archigen: Research Funding; Roche: Other: Travel/Accommodations/Expenses, Research Funding; Bayer: Research Funding; AstraZeneca: Research Funding; Takeda: Honoraria, Other: Travel/Accommodations/Expenses, Research Funding; Pfizer: Research Funding; BMS: Other: Travel/Accommodations/Expenses; Abbvie: Other: Travel/Accommodations/Expenses, Research Funding; Jazz: Other: Travel/Accommodations/Expenses; Abdi Ibrahim: Other: Travel/Accommodations/Expenses; Sanofi: Other: Travel/Accommodations/Expenses; MSD: Research Funding. Perini: Takeda: Speakers Bureau; Roche: Consultancy, Speakers Bureau; AstraZeneca: Consultancy, Speakers Bureau; Abbvie: Consultancy, Other: Travel/Accommodations/Expenses, Speakers Bureau; MSD: Consultancy, Speakers Bureau; Janssen: Consultancy, Other: Travel/Accommodations/Expenses, Speakers Bureau. Salles: Debiopharm: Consultancy; Incyte: Consultancy; Morphosys: Consultancy, Honoraria; Janssen: Consultancy; Epizyme: Consultancy, Honoraria; Rapt: Consultancy; Loxo: Consultancy; Ipsen: Consultancy; Miltneiy: Consultancy; Regeneron: Consultancy, Honoraria; Allogene: Consultancy; Velosbio: Consultancy; Takeda: Consultancy; Genmab: Consultancy; Genentech/Roche: Consultancy; Kite/Gilead: Consultancy; Novartis: Consultancy; BMS/Celgene: Consultancy; Beigene: Consultancy; Abbvie: Consultancy, Honoraria; Bayer: Honoraria. Shipp: Bayer: Other: Institution: Research Grant/Funding; AstraZeneca: Consultancy, Research Funding; Abbvie: Other: Institution: Research Grant/Funding; Immunitas Therapeutics: Consultancy; Merck: Research Funding; Bristol Myers Squibb: Research Funding. Thompson: Merck & Co., Inc.: Current Employment, Other: Current Stockholder. Chakraborty: Merck & Co., Inc.: Current Employment, Other: Current Stockholder. Marinello: Merck & Co., Inc.: Current Employment, Other: Current Stockholder. Armand: Merck: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy; Affimed: Consultancy, Research Funding; Adaptive: Consultancy, Research Funding; Infinity: Consultancy; ADC Therapeutics: Consultancy; Celgene: Consultancy; Morphosys: Consultancy; Daiichi Sankyo: Consultancy; Miltenyi: Consultancy; Tessa: Consultancy; GenMab: Consultancy; C4: Consultancy; Enterome: Consultancy; Regeneron: Consultancy; Epizyme: Consultancy; AstraZeneca: Consultancy; Genentech: Consultancy, Research Funding; Roche: Research Funding; Tensha: Research Funding; Otsuka: Research Funding; Sigma Tau: Research Funding; IGM: Research Funding; Kite: Research Funding.