UNMET NEED IN RELAPSED/REFRACTORY (R/R) MANTLE CELL LYMPHOMA (MCL) POST‐BRUTON TYROSINE KINASE INHIBITOR (BTKI): A SYSTEMATIC LITERATURE REVIEW AND META‐ANALYSIS

Abstract

Background: Most patients with MCL, a rare B-cell non-Hodgkin lymphoma, will relapse or become refractory to treatment. While the introduction of BTKis has been transformative, options for patients who fail to respond or whose disease progresses on BTKis remain limited and largely palliative in nature. We sought to characterize and quantify the unmet clinical need of patients with R/R MCL in the post-BTKi setting. Methods: MEDLINE, Embase, and CENTRAL were systematically searched to October 2022—supplemented with hand searches of select conferences—to identify studies reporting overall survival (OS), progression-free survival (PFS), and/or response outcomes of patients receiving non-CAR-T treatments or brexucabtagene autoleucel (brexu-cel) in the post-BTKi setting. Random effects bivariate meta-analyses of OS/PFS were conducted based on studies with published Kaplan-Meier (KM) curves from which individual patient data could be estimated. Response outcomes, based on the best response achieved, were meta-analyzed using a generalized linear mixed model. Outcomes were evaluated separately for patients treated with non-CAR-T and brexu-cel. Results: Twenty-six studies (23 observational; 3 trials), reporting the outcomes of 1845 patients treated from 2005 to 2022, were included, where patients were initially enrolled for treatment with a BTKi (12 studies) or for treatment post-BTKi (14 studies). The non-CAR-T interventions varied, with most studies reporting outcomes from cohorts of patients receiving a variety of interventions. Across the included studies, most patients were male (65-94%) and older, with the median age varying from 63 to 77 years. OS and PFS KM curves were published in 10 and 3 studies, respectively, for non-CAR-T outcomes. The pooled median OS/PFS for these patients was 9.1 and 7.6 months, respectively (Table 1). The pooled objective response rate (ORR) and percentage of patients achieving a complete response (CR) were 45% and 23%, respectively. The median OS/PFS of patients who received brexu-cel was 32.1 and 14.9 months, based on 5 and 6 studies with KM curves, respectively, with ORR/CR rates of 89% and 74%. Analyses were not sensitive to different survival distributions or fixed/random effects models. Conclusions: Treatment options in the post-BTKi setting are heterogeneous and a significant unmet clinical need persists. Though longer follow-up is needed for survival outcomes, treatment with brexu-cel is emerging as a promising option in this difficult-to-treat setting. The research was funded by: This study was funded by Kite, a Gilead company. Keywords: Aggressive B-cell non-Hodgkin lymphoma, Cellular therapies Conflicts of interests pertinent to the abstract M. Dreyling Consultant or advisory role Astra Zeneca, Beigene, BMS/Celgene, Gilead/Kite, Janssen, Lilly/Loxo, Novartis, Roche Research funding: Abbvie, Bayer, BMS/Celgene, Gilead/Kite, Janssen, Roche Educational grants: Janssen, Roche Other remuneration: Astra Zeneca, Gilead/Kite, Janssen, Lilly, Novartis, Roche B. Shah Consultant or advisory role Pepromene Bio; Takeda Honoraria: Kite/Gilead; BMS; Novartis; Amgen; Pfizer; Beigene; Adaptive; Century Therapeutics; Autolus Research funding: Kite; Servier; Jazz Pharma Educational grants: Kite/Gilead; Takeda Other remuneration: Chair, NCCN Adult ALL subcommittee J. Wu Employment or leadership position: Kite, a Gilead company Stock ownership: Gilead; Amgen; Abbott; AbbVie; Avid; Curis; Viracta T. Itani Employment or leadership position: Kite, a Gilead company Stock ownership: Gilead Sciences M. J. Zoratti Research funding: RainCity Analytics has received funds from for-profit healthcare companies for research S. Kanters Research funding: RainCity Analytics has received funds from for-profit healthcare companies for research S. W. Wade Consultant or advisory role Kite Pharma; Amgen; Allergan/Abbvie; Johnson & Johnson W. Peng Employment or leadership position: Kite, a Gilead company Stock ownership: Gilead J. Castaigne Employment or leadership position: Kite, a Gilead company Stock ownership: Gilead I. Kloos Employment or leadership position: Kite, a Gilead company Stock ownership: Gilead Sciences M. Wang Consultant or advisory role AbbVie; Acerta Pharma; ADC Therapeutics America; Amphista Therapeutics Limited; AstraZeneca; Be Biopharma; BeiGene; BioInvent; Deciphera; DTRM Biopharma (Cayman) Limited; Genentech; InnoCare; Janssen; Kite Pharma; Leukemia & Lymphoma Society; Lilly; Merck; Miltenyi Biomedicine; Milken Institute; Oncternal; Parexel; Pepromene Bio; Pharmacyclics; VelosBio Honoraria: AbbVie; Acerta Pharma; AstraZeneca; Bantam Pharmaceutical; BeiGene; BioInvent; Bristol Myers Squibb; CAHON; Dava Oncology; Eastern Virginia Medical School; Genmab; i3Health; IDEOlogy Health; Janssen; Kite Pharma; Leukemia & Lymphoma Society; Medscape; Meeting Minds Experts; MD Education ; MJH Life Sciences; Merck; Moffit Cancer Center; Nurix; Oncology Specialty Group; OncLive; Pharmacyclics; Physicians Education Resources (PER); Practice Point Communications (PPC); Studio ER Congressi Research funding: Acerta Pharma; AstraZeneca; BeiGene; BioInvent; Celgene; Genmab; Genentech; Innocare; Janssen; Juno Therapeutics; Kite Pharma; Lilly; Loxo Oncology; Molecular Templates; Oncternal; Pharmacyclics; VelosBio; Vincerx