Session: 626. Aggressive Lymphomas: Prospective Therapeutic Trials: Frontline Treatment of Large B-cell Lymphoma
Hematology Disease Topics & Pathways:
Research, clinical trials, Biological therapies, Lymphomas, non-Hodgkin lymphoma, Bispecific Antibody Therapy, Clinical Research, Diseases, aggressive lymphoma, Therapies, Lymphoid Malignancies
Methods: Eligible pts were aged ≥80 years, or 60–79 years with ≥1 activity of daily living (ADL) or instrumental ADL impaired, or reduced cardiac, renal, or liver function precluding the use of full-dose CIT. Pre-phase prednisone with or without vincristine was allowed. Pts received Cycle (C) 1 step-up dosing with IV Mosun on Days (D) 1 (1mg), 8 (2mg) and 15 (13.5 or 30mg) and 13.5mg or 30mg Mosun on D1 of each subsequent 21-day cycle (1/2/13.5mg and 1/2/30mg). Pts with a complete response (CR) stopped Mosun after 8 cycles; pts with a partial response (PR) or stable disease (SD) could continue Mosun up to 17 cycles. Primary endpoints included objective response and CR rates (assessed by PET-CT). Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were assessed by ASTCT criteria (Lee et al. Biol Blood Marrow Transplant 2019). Tumor biomarkers were assessed by immunohistochemistry. Pts enrolled in two safety-evaluation cohorts received Mosun 1/2/13.5mg or 1/2/30mg, and pts in the expansion phase received Mosun 1/2/30mg (enrollment completed July 2021). Here, we report combined data for the two doses.
Results: As of June 01, 2022, 54 pts had received Mosun (13.5mg, n=8; 30mg, n=46) and all were efficacy evaluable. Median age was 83 years (range: 65–100), 33 (61%) pts were female, 35 (65%) had an ECOG PS 0–1, 30 (56%) had Ann Arbor Stage III–IV, and 44 (81%) had an International Prognostic Index score ≥2. Median number of cycles received was eight (range: 1–16); three pts in PR continued treatment after C8. Median follow-up was 23.3 months (range: 0‒36). Best overall response rates (ORR) and CR rates were 56% (30/54) and 43% (23/54), respectively. Responses following EOT (primary response assessment timepoint) in both dosing cohorts combined were: ORR, 43% (23/54); CR, 35% (19/54); PR, 7% (4/54); SD, 2% (1/54); progressive disease, 33% (18/54). Median duration of CR was 15.8 months (95% CI: 8.5–not estimable); of 23 pts who achieved a CR (at any timepoint), CR was maintained in 11 pts for >12 months (Figure). The 12-month progression-free survival rate was 39% (95% CI: 25.8–52.8). No new safety signals were observed; 98% of pts had ≥1 adverse event (AE); 48% had a grade (gr) 3/4 AE. An AE leading to treatment discontinuation was reported in one patient (renal failure; not related to Mosun). Fatal AEs occurred in three pts; one death from natural causes and two due to COVID-19 pneumonia (none considered Mosun-related). Common (>10%) treatment-emergent AEs were rash (31%), CRS (26%), and fatigue (26%). Ten pts had gr 1 CRS and four had gr 2. No gr 3+ CRS and no new CRS were reported since the previous cut-off. Neutropenia was reported in 15% of pts (gr 2, 2%; gr 3/4, 13%), and gr 3 febrile neutropenia was reported in one patient. Median duration of neutropenia was 12 days (range: 7‒28). Serious infections were reported in 22% of pts (gr 3, 17%; gr 5, 4% [all due to COVID-19 pneumonia]). No ICANS related to Mosun were reported. Exploratory biomarker analyses of tumor composition revealed increased levels of CD8+ T cells at baseline in responders vs non-responders.
Conclusions: Mosun monotherapy continued to demonstrate promising efficacy with durable responses and a manageable safety profile. These data support a potential future role for Mosun in elderly/unfit pts with previously untreated DLBCL and may help to identify pts whose tumors respond to treatment with bispecific antibody monotherapy.
Disclosures: Olszewski: Adaptive Biotechnologies and Genentech: Research Funding; Genmab, Schrodinger, Blue Cross and Blue Shield of Rhode Island and TG Therapeutics: Consultancy; Brown Physicians, Inc.: Current Employment. Avigdor: Takeda, Gilead, Novartis, Roche, BMS: Consultancy; AbbVie: Honoraria. Babu: Lutheran Hospital: Current holder of stock options in a privately-held company; Fort Wayne Medical Oncology & Hematology: Current Employment, Current holder of stock options in a privately-held company; BMS, Alexion Pharmaceuticals, Lilly, Janssen Oncology, Genentech/Roche: Other: travel, accommodations, expenses; Alexion: Speakers Bureau; BMS, Novartis, Genentech/Roche, AstraZeneca/MedImmune, Janssen Oncology, Amgen, TG Therapeutics, AbbVie, Lilly, Alexion Pharmaceuticals, Nektar, Sanofi, Argenx, Syndax: Research Funding; BMS, AstraZeneca, Castle Biosciences, Pharmacosmos, Beigene, Kite, Amgen: Honoraria; BMS, AstraZeneca, Argenx, Boehringer Ingelheim, Bayer, Kite Pharma, Janssen Oncology, Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees. Levi: Abbvie: Consultancy, Honoraria. Eradat: Genentech: Consultancy, Honoraria, Research Funding, Speakers Bureau; ATARA: Research Funding; Gilead: Research Funding; Incyte: Consultancy, Honoraria, Research Funding, Speakers Bureau; Beigene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Morphosys: Consultancy, Honoraria, Research Funding, Speakers Bureau; Pharmacyclics: Honoraria, Research Funding; Kite: Research Funding; AstraZeneca: Research Funding; Celgene: Research Funding; BMS: Research Funding; Juno: Research Funding; AbbVie: Consultancy, Honoraria, Research Funding, Speakers Bureau. Holmes: Karyopharm, Kite, Rigel, Seattle Genetics: Speakers Bureau; Exuma Biotech: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers, Kite: Honoraria; ADC Therapeutics, Adicet Bio, Artiva, Autolus, Bristol-Myers, Caribou Biosciences, Exuma Biotech, Genentech, Incyte, Kite, Novartis: Research Funding; ADC Therapeutics, Astra-Zeneca, Bristol-Myers, Crispr Therapeutics, Epizyme, Janssen, Karyopharm, Kite, Novartis, Rigel, TG Therapeutics: Consultancy. McKinney: Kite/Gilead, Seattle Genetics, Molecular Templates, BTG, Pharmacyclics, Verastem, Genentech, Celgene: Honoraria; UNUM, Molecular Templates, Incyte, Beigene, Denovo Biopharma, Pharmacyclics, Nordic Nanovector, BMS, Genentech, Celgene, Atara, LOXO, Cellactor: Research Funding; Genentech, Epizyme, Pharmacyclics, Celgene: Consultancy; Kite/Gilead, ADC therapeutics: Speakers Bureau. Woszczyk: Abbvie, Celgene/BMS: Honoraria; Abbvie, Acerta Pharma, Agios Pharm, Astellas, Celgene/BMS, Janssen-Cliag, Kartos Therapeutics, LoxoOnc, Novartis, Roche: Other: Participation in clinical trials sponsored by. Giannopoulos: Roche, Sanofi, Takeda, Janssen, Abbvie, Celgene, Amgen: Honoraria, Research Funding. Jurczak: TG Therapeutics: Research Funding; Lilly: Consultancy, Research Funding; Takeda: Research Funding; AbbVie: Consultancy, Research Funding; Roche: Consultancy, Research Funding; Bayer: Research Funding; Beigene: Consultancy, Research Funding; Merck: Research Funding; Sandoz: Consultancy, Research Funding; Celgene: Research Funding; Loxo Oncology: Consultancy, Research Funding; Novo Nordisk: Research Funding; Morphosys: Research Funding; Mei Pharma: Research Funding; AstraZeneca: Consultancy, Research Funding; Janssen: Consultancy, Research Funding. Dunshee: Genentech, Inc.: Current Employment. Yang: Genentech / Roche: Current Employment, Current equity holder in private company, Current holder of stock options in a privately-held company. Zhou: F. Hoffmann La Roche, Ltd.: Current Employment; FibroGen, Inc.: Ended employment in the past 24 months. Qayum: Roche: Current Employment, Current equity holder in publicly-traded company. Sellam: F. Hoffmann La Roche, Ltd.: Current Employment, Current holder of stock options in a privately-held company.
OffLabel Disclosure: Mosunetuzumab is a CD20xCD3 bispecific antibody that redirects T cells to engage and eliminate malignant B cells. Mosunetuzumab is an investigational agent in the United States.
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