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3093 Outcomes of Relapsed or Refractory Diffuse Large B-Cell Lymphoma Treated with R-GemOx: A Multi-Center Retrospective Cohort Study

Program: Oral and Poster Abstracts
Session: 626. Aggressive Lymphomas: Clinical and Epidemiological: Poster II
Hematology Disease Topics & Pathways:
Research, Clinical Research, Real-world evidence
Sunday, December 8, 2024, 6:00 PM-8:00 PM

Samuel Yamshon, MD1*, Jean L. Koff, MD, MSc2, Melissa C. Larson, MS3*, Brad S. Kahl, MD4, Carla Casulo, MD5, Izidore S. Lossos, MD6, Sara Haddadi6*, Michele D. Stanchina, DO, MS7, Dai Chihara, MD, PhD8, Amy A. Ayers, MPH8*, Thomas M. Habermann, MD9, Yucai Wang, MD, PhD9, Arushi Khurana, MBBS9, Grzegorz S. Nowakowski, MD9, Tanner W Reicks3*, Umar Farooq, MD10, Brian K. Link, MD10*, Jonathon B. Cohen, MD, MS11, Peter Martin, MD12, Jia Li, PhD13*, Ashwini Shewade13*, Connie Lee Batlevi, MD, PhD13*, Andrea Lo-Rossi, PhD13*, David Fox13*, Anthony Masaquel13*, Yong Mun13*, James R. Cerhan, MD, PhD3, Christopher R. Flowers, MD, MS8, Matthew J. Maurer, DSc3 and Loretta Nastoupil8*

1Department of Hematology & Medical Oncology, NewYork-Presbyterian/Weill Cornell Medical Center, New York, NY
2Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Atlanta, GA
3Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN
4Department of Medicine, Washington University School of Medicine, St. Louis, MO
5Division of Hematology and Medical Oncology, Wilmot Cancer Institute, University of Rochester, Rochester, NY
6Division of Hematology, Sylvester Comprehensive Cancer Center, Miami, FL
7Sylvester Comprehensive Cancer Center, Division of Hematology, University of Miami, Miller School of Medicine, Miami, FL
8Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX
9Division of Hematology, Mayo Clinic, Rochester, MN
10Division of Hematology, Oncology, and Blood & Marrow Transplantation, University of Iowa, Iowa City, IA
11Winship Cancer Institute, Emory University, Atlanta, GA
12Division of Hematology and Medical Oncology, Weill Cornell Medicine, New York, NY
13Genentech, Inc., South San Francisco, CA

Background: Rituximab, gemcitabine, and oxaliplatin (R-GemOx) is a commonly utilized chemoimmunotherapy regimen for relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL), especially for patients ineligible for autologous stem cell transplant (ASCT) or chimeric antigen receptor T cell therapy (CAR T). R-GemOx is used as a comparator arm in several active phase III clinical trials for R/R DLBCL, including the POLARGO (polatuzumab vedotion and R-GemOx), STARGLO (glofitamab and GemOx), SUNMO (mosunetuzumab and polatuzumab vedotin), LOTIS-5 (loncastuximab tesirine and rituximab), and EPCORE DLBCL-1 (epcoritamab) studies. However, real-world data are limited to understand the patterns of use and outcomes of R-GemOx in the US.

Methods: We developed a retrospective multicenter US cohort (known as LEO CReWE) of patients with R/R DLBCL and other aggressive B-cell lymphomas at the eight US academic centers participating in the LEO Cohort Study (NCT02736357). Patients first diagnosed with DLBCL (including transformed and high-grade B-cell lymphoma) from 2007 - 2022 who received second line (2L) or later therapy for R/R DLBCL with R-GemOx were included. Baseline characteristics, treatment, and follow-up data were abstracted by chart review. Index line of therapy was defined as the first receipt of R-GemOx therapy in the 2L or later setting. Intent for CAR T and/or ASCT was evaluated at each line of therapy based on medical records at the time of treatment initiation. Subgroup analyses were pre-planned in groups of special interest, including those treated with R-GemOx without intent for ASCT or CAR T, those treated as a bridge to CAR T, and those aged 70 and older.

Results: 183 patients with R/R DLBCL treated with R-GemOx were included. At time of initiation of R-GemOx, median age was 68 years (range 21-88), with 71 patients (39%) aged 70+ and 18 (10%) aged 80+. Many patients had high risk features including 13% with high grade B-cell lymphoma and 56% with IPI 3 or greater. 21% had an ECOG performance status of 2 or greater. Patients received a median of 2 lines of therapy prior to the index line of R-GemOx (range 1-7). 52% of patients did not achieve a complete response (CR) to first-line therapy, and 20% relapsed <12 months from an initial CR. In all patients receiving R-GemOx, the overall response rate (ORR) was 45% (29% CR). At a median follow-up of 39 months, median EFS was 2.3 months (95% CI: 1.8-3.2), with 12-month EFS of 21% and a 24-month EFS of 15%. Median OS was 13.5 months (95% CI: 9.6-18.1), with a 12-month OS of 52% and a 24-month OS of 38%. In patients treated without intent for ASCT or CAR T, ORR was 33% (18% CR). Median EFS was 2.0 months (95% CI: 1.6-2.5) with 12- and 24-month EFS of 14% and 9%, respectively. Median OS was 9.5 months (95% CI: 6.6-16.1) with 12- and 24-month OS of 45% and 29%, respectively. In patients receiving R-GemOx as bridging to ASCT or CAR T, ORR was 57% (35% CR). 35% received CAR T and 14% received ASCT, while the remainder did not receive the intended therapy as part of this line. Median EFS was 3.6 months (95% CI: 1.8-5.2) with 12- and 24-month EFS of 28% and 25%, respectively. Median OS was 17.4 months (95% CI: 13.4-NR); 12- and 24-month OS were 61% and 50%, respectively. In patients aged 70+, ORR was 53% (33% CR). Median EFS was 2.3 months (95% CI: 1.6-5.2), with 12- and 24-month EFS of 20% and 18%, respectively. Median OS was 13.9 months (95% CI: 8.6-30.2); 12- and 24-month OS were 57% and 39%, respectively.

Conclusion: This study represents the largest reported cohort of patients treated with R-GemOx in US academic centers to date. The ORR of 45% and CR rate of 29% CR, as well as median EFS and OS of 2.3 and 13.5 months, respectively, are consistent with findings from previous phase II studies; these results highlight that responses to R-GemOx are not durable and the vast majority of patients require additional therapy. This study demonstrates real-world evidence of the efficacy of R-GemOx in a large cohort of patients with R/R DLBCL from the US over a long period, including both transplant-eligible and -ineligible patients, and patients treated in the CAR T era. These data aid in providing a benchmark for active clinical trials in the rapidly evolving landscape of R/R DLBCL therapies and allow potential comparison to a real-world cohort of patients with a broad range of clinical characteristics.

Disclosures: Yamshon: Kite Pharma: Consultancy; Bristol Myers Squibb: Consultancy. Koff: Viracta Therapeutics: Research Funding; BeiGene: Consultancy; AbbVie: Consultancy. Kahl: BeiGene: Consultancy, Research Funding; Lilly: Consultancy, Honoraria; AbbVie: Consultancy; Roche: Consultancy, Research Funding; ADCT: Consultancy; AstraZeneca: Consultancy, Research Funding; Genentech: Consultancy; Bristol Myers Squibb: Consultancy, Honoraria. Casulo: Genentech: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria; Gilead Sciences, Secura Bio: Research Funding; Verastem: Research Funding; Genmab: Research Funding; Bristol Myers Squibb: Consultancy, Honoraria, Research Funding. Lossos: University of Miami: Current Employment; ADCT: Research Funding; Not specified: Patents & Royalties. Chihara: BeiGene: Honoraria; Genmab: Research Funding; Genentech: Research Funding; Ono pharmaceutical: Research Funding; SymBio pharmaceutical: Honoraria; BMS: Research Funding. Habermann: Lilly: Other: Data Monitoring Committee. Wang: Eli Lilly, LOXO Oncology, TG Therapeutics, Incyte, InnoCare, Kite, Jansen, BeiGene, AstraZeneca, Genmab, AbbVie: Other: Advisory Board; InnoCare, AbbVie: Consultancy; Incyte, InnoCare, LOXO Oncology, Eli Lilly, MorphoSys, Novartis, Genentech, Genmab, AbbVie, BeiGene, Merck: Research Funding; Kite: Honoraria. Nowakowski: Incyte Corporation: Consultancy; Selvita Inc: Consultancy; MEI Pharma: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; Kymera Therapeutics: Consultancy; Segen: Consultancy; F. Hoffmann-La Roche Limited: Consultancy; ADC Therapeutics: Consultancy; Celgene Corporation: Consultancy, Research Funding; Genentech: Consultancy; Constellation Pharmaceuticals: Consultancy; Daiichi Sankyo: Consultancy; Blueprint Medicines Corporation: Consultancy; Debiopharm: Consultancy; Curis: Consultancy, Research Funding; Karyopharm Therapeutics: Consultancy; Zai Laboratory: Consultancy; MorphoSys AG: Consultancy, Research Funding; Bantam Pharmaceutical, LLC: Consultancy; TG Therapeutics Inc: Consultancy; Ryvu Therapeutics: Consultancy; AbbVie Inc.: Consultancy; Fate Therapeutics: Consultancy. Reicks: Genentech: Research Funding. Farooq: Caribou, MorphoSys: Consultancy; Caribou, Gilead/Kite: Honoraria; Regeneron: Research Funding. Link: Genentech: Research Funding. Cohen: Hutchmed: Consultancy, Research Funding; Astra Zeneca: Consultancy, Research Funding; Takeda: Research Funding; Genentech: Research Funding; Nurix: Research Funding; Beigene: Consultancy; Janssen: Consultancy; Lilly: Consultancy, Research Funding; Kite/Gilead: Consultancy. Martin: AbbVie, AstraZeneca, Beigene, Daiichi Sankyo, Genentech, Janssen, Merck, Pepromene: Consultancy. Li: Genentech: Current Employment. Shewade: Roche Holding AG: Current equity holder in publicly-traded company; Genentech, Inc.: Current Employment. Batlevi: F. Hoffmann-La Roche Ltd/Genentech, Inc.: Current Employment; Memorial Sloan Kettering Cancer Center: Ended employment in the past 24 months; BMS, Seattle Genetics, Kite, Karyopharm, TG Therapeutics, ADC Therapeutics, AbbVie, Genentech, Inc., Treeline Bioscience: Consultancy; F. Hoffmann-La Roche Ltd/Genentech, Inc.: Current equity holder in publicly-traded company; Regeneron, Moderna: Divested equity in a private or publicly-traded company in the past 24 months; Epizyme, Autolus, F. Hoffmann-La Roche Ltd, Vincerx: Research Funding; Dava Oncology, TouchIME, Medscape: Honoraria. Lo-Rossi: Genentech/Roche: Current Employment, Current holder of stock options in a privately-held company. Fox: F. Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company; Genentech, Inc.: Current Employment. Masaquel: F. Hoffmann-La Roche Ltd: Current holder of stock options in a privately-held company; Genentech, Inc.: Current Employment. Mun: Genentech, Inc.: Current Employment; F. Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company. Cerhan: Protagonist Therapeutics: Other: SMC; GenMab: Research Funding; Genentech: Research Funding; BMS: Research Funding. Flowers: Xencor: Research Funding; Bristol Myers Squibb: Consultancy; Amgen: Research Funding; Sanofi: Research Funding; Pharmacyclics: Research Funding; Cancer Prevention and Research Institute of Texas: CPRIT Scholar in Cancer Research: Research Funding; Nektar: Research Funding; Allogene: Research Funding; Novartis: Research Funding; Eastern Cooperative Oncology Group: Research Funding; Ziopharm National Cancer Institute: Research Funding; Genmab: Consultancy; N-Power Medicine: Consultancy, Current holder of stock options in a privately-held company; Bio Ascend: Consultancy; 4D: Research Funding; Guardant: Research Funding; Morphosys: Research Funding; Kite: Research Funding; Foresight Diagnostics: Consultancy, Current holder of stock options in a privately-held company; Celgene: Consultancy, Research Funding; Adaptimmune: Research Funding; Acerta: Research Funding; Karyopharm: Consultancy; EMD Serono: Research Funding; Genentech/Roche: Consultancy, Research Funding; Burroughs Wellcome Fund: Research Funding; Takeda: Research Funding; Pfizer: Research Funding; Pharmacyclics / Janssen: Consultancy; Seagen: Consultancy; Spectrum: Consultancy; Gilead: Consultancy, Research Funding; Cellectis: Research Funding; BostonGene: Research Funding; AbbVie: Consultancy, Research Funding; BeiGene: Consultancy; Bayer: Consultancy, Research Funding; TG Therapeutics: Research Funding; Denovo Biopharma: Consultancy; Iovance: Research Funding; Janssen Pharmaceuticals: Research Funding; AstraZeneca: Consultancy. Maurer: GenMab: Research Funding; Roche/Genentech: Research Funding; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Research Funding. Nastoupil: Gilead Sciences/Kite Pharma: Honoraria, Research Funding; Abbvie, BMS, Caribou Biosciences, Genentech, Genmab, Gilead/Kite, Janssen, Incyte, Ipsen, Merck, Novartis, Regeneron, Takeda: Consultancy; Caribou Biosciences: Honoraria, Research Funding; Daiichi Sankyo: Honoraria, Research Funding; Genentech: Honoraria, Research Funding; BMS: Honoraria, Research Funding; Denovo Biopharma: Honoraria; Novartis: Honoraria, Research Funding; Genmab: Honoraria, Research Funding; Merck: Honoraria, Research Funding; Incyte Corporation: Honoraria; Janssen: Honoraria, Research Funding; Regeneron: Consultancy, Honoraria; BMS, Caribou Biosciences, Daiichi Sankyo, Genentech, Genmab, Gilead/Kite, Janssen, Incyte, Ipsen, Merck, Novartis, Takeda: Research Funding; Takeda: Consultancy, Honoraria, Research Funding; AbbVie: Honoraria; ADC Therapeutics: Honoraria; Abbvie, BMS, Caribou Biosciences, Daiichi Sankyo, Genentech, Genmab, Gilead/Kite, Janssen, Incyte, Ipsen, Novartis, Takeda: Honoraria.

*signifies non-member of ASH