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

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.

Yamshon:Kite Pharma: Consultancy; Bristol Myers Squibb: Consultancy. Koff:Viracta Therapeutics: Research Funding; BeiGene: Consultancy; AbbVie: Consultancy. Kahl:ADCT: Consultancy; Roche: Consultancy, Research Funding; Novartis: Consultancy; AstraZeneca: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy; Genentech: Consultancy; Kite: Consultancy; Lilly: Consultancy; Merck: Consultancy; AbbVie: Consultancy; BeiGene: Consultancy, Research Funding. 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:Ono pharmaceutical: Research Funding; SymBio pharmaceutical: Honoraria; BeiGene: Honoraria; Genmab: Research Funding; MorPhosys: Research Funding; 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.