Retrospective Analysis of Gemcitabine and Oxaliplatin (GemOx)-Based Treatment in Patients with Relapsed/Refractory Aggressive B-Cell Non-Hodgkin Lymphoma
Authors: Schade Jake R. , Kim Charles , Drill Esther , Qiu Annie , Batlevi Connie Lee , Caron Philip , Colbourn Donald Steven , Hamilton Audrey , Hamlin Paul A. , Horwitz Steven M. , Intlekofer Andrew M. , Joffe Erel , von Keudell Gottfried R. , Kumar Anita , Noy Ariela , Okwali Michelle , Owens Colette , Palomba M. Lia , Rodriguez-Rivera Ildefonso , Sauter Craig S. , Schoder Heiko , Straus David J. , Vardhana Santosha , Younes Anas , Zelenetz Andrew D. , Matasar Matthew J 
Published: November 2019

Introduction: Gemcitabine/oxaliplatin (GemOx), with or without rituximab, is a frequently used treatment of relapsed or refractory (r/r) aggressive B-cell non-Hodgkin lymphoma (B-NHL), and is NCCN compendium-listed for both transplant-eligible and ineligible patients based upon results in small phase II clinical trials. Increasingly, GemOx is being accepted as a comparator arm for clinical trials in these populations. However, there is a paucity of observational data describing the effectiveness of R-GemOx in the treatment of r/r aggressive B-cell lymphoma.

Methods: We conducted a retrospective analysis of the use of the GemOx regimen (with or without rituximab) in patients with r/r aggressive B-NHL at Memorial Sloan Kettering Cancer Center between January 2007 and January 2018, with a data cutoff of July 1, 2019. Data were extracted from the electronic medical record. Eligible diagnoses included diffuse large B-cell lymphoma and its subtypes (DLBCL); high-grade B-cell lymphomas (HGBL); transformed indolent B-cell lymphoma (tNHL) and grade 3B follicular lymphoma (FL3B). The primary objective of the study was to evaluate the activity of GemOx-based treatment in this patient population, as measured by overall response rate (ORR), complete response (CR) rate, progression-free survival (PFS), and overall survival (OS). CR was defined by a qualitatively negative 18-FDG-PET scan following completion of GemOx. PFS was defined as the time from start of therapy to disease progression or death, censoring patients at the time of initiation of any consolidative treatment. Similarly, OS was defined as the time from the start of GemOx until death or loss to follow-up.

Results: Data were collected for 140 consecutive patients that received GemOx with (n=81) or without (n=59) rituximab in the treatment of a qualifying diagnosis (Table 1). Those treated had a median age at initiation of therapy of 69 (range, 30-92) and were predominantly male (58%). The median number of prior lines of therapy was 1 (range, 1-7), and the majority (97%) had received prior rituximab; few had received either prior autotransplant (11%) or allotransplant (1%). Regarding treatment delivered, the median number of cycles of therapy was 2 (range 1-12) with a mode of 2 (n=44, 31%). The ORR was 26% (n=37) with a CR rate of 15% (n=21). When evaluated by diagnosis, the ORR was 22% (n=19/88) in DLBCL, 40% (n=4/10) in HGBL, 35% (n=14/40) in tNHL, and 0% (n=0/2) in FL3B. Of the patients that responded to GemOx, 11 were successfully bridged to transplant (7 auto; 4 allo); two of those who went on to allotransplant had previously undergone autotransplant. Additionally, 3 patients went on to subsequently receive CAR-T therapy. Assessing the cohort overall, with a median follow-up of 48.1 months, PFS was only 1.4 months (95% CI: 1.3, 1.8), and median OS was 7.8 months (95% CI: 5.5, 12.0) (Figure 1). OS was longest for patients with tNHL at 10.2 months followed by DLBCL (7.5), HGBL (6.8) and FL3B (4.1) (Figure 2). Patients that received GemOx without rituximab in the setting of rituximab-refractory disease had a median OS of 4.1 months, less than that of 10.7 months for those receiving rituximab (p=0.052). However, there was no difference observed in PFS by inclusion of rituximab (1.6 months vs. 1.3 months, p=0.166). Patients with disease that was primary refractory following first-line therapy had a median OS of 4.5 months from initiation of GemOx, less than that of 10.8 months for patients that had achieved complete remission with first-line therapy (p=0.024). Patients that received GemOx as second-line therapy did not have a statistically significantly higher ORR (31% vs. 19%), OS (10.8 vs. 6.0 months), or PFS (1.7 vs, 1.4 months; all p=NS). In the subset of patients with DLBCL, there was again no significant difference in ORR (21% vs. 22%, p=NS), OS (8.5 vs. 6.1 months), or PFS (1.6 vs. 1.4 months; all p=NS).

Conclusion: Despite compendium listing for both transplant-eligible and ineligible patients, and despite its adoption as a comparator arm in current and planned trials in r/r DLBCL, the real-world activity of GemOx with or without rituximab in the treatment of relapsed or refractory aggressive B-cell lymphoma is poor. Ongoing analysis is being conducted to seek clinical and histopathologic features associated with improved outcomes with GemOx.

Disclosures

Batlevi: Juno Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees. Colbourn:GILD: Other: Stock; LLY: Other: Stock; JNJ: Other: Stock; SGEN: Other: Stock; MRK: Other: Stock; SNY: Other: Stock; BIIB: Other: Stock; ABBV: Other: Stock; CELG: Other: Stock. Horwitz:Infinity/Verastem: Consultancy, Research Funding; Trillium: Research Funding; Infinity/Verastem: Consultancy, Research Funding; Kyowa Hakko Kirin: Consultancy; Corvus Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Millennium/Takeda: Consultancy, Research Funding; Mundipharma: Consultancy; Portola: Consultancy; Celgene: Consultancy, Research Funding; Portola: Consultancy; Innate Pharma: Consultancy; Seattle Genetics: Consultancy, Research Funding; Infinity/Verastem: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Kura: Consultancy; Aileron: Research Funding; Corvus Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Corvus Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Forty-Seven: Research Funding; Celgene: Consultancy, Research Funding; ADCT Therapeutics: Research Funding; Kyowa Hakko Kirin: Consultancy; ADCT Therapeutics: Research Funding; Astex: Consultancy; Mundipharma: Consultancy; Miragen: Consultancy; Portola: Consultancy; Mundipharma: Consultancy; Seattle Genetics: Consultancy, Research Funding; Innate Pharma: Consultancy; Innate Pharma: Consultancy; Affimed: Consultancy; Affimed: Consultancy; Innate Pharma: Consultancy; Aileron: Research Funding; Kyowa Hakko Kirin: Consultancy; Forty-Seven: Research Funding; Kura: Consultancy; Millennium/Takeda: Consultancy, Research Funding; Forty-Seven: Research Funding; ADCT Therapeutics: Research Funding; Seattle Genetics: Consultancy, Research Funding; Astex: Consultancy; Aileron: Research Funding; Portola: Consultancy; Astex: Consultancy; Celgene: Consultancy, Research Funding; Trillium: Research Funding; Miragen: Consultancy; Trillium: Research Funding; Kyowa Hakko Kirin: Consultancy; Mundipharma: Consultancy; Millennium/Takeda: Consultancy, Research Funding; Trillium: Research Funding; Aileron: Research Funding; Affimed: Consultancy; Corvus Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Millennium/Takeda: Consultancy, Research Funding; Astex: Consultancy; Miragen: Consultancy; Miragen: Consultancy; Affimed: Consultancy; Celgene: Consultancy, Research Funding; Kura: Consultancy; Kura: Consultancy; ADCT Therapeutics: Research Funding; Forty-Seven: Research Funding; Infinity/Verastem: Consultancy, Research Funding. von Keudell:Bayer: Consultancy; Genentech: Consultancy; Pharmacyclics: Consultancy; Pharmacyclics: Consultancy; Bayer: Consultancy; Genentech: Consultancy. Kumar:Seattle Genetics: Research Funding. Noy:Medscape: Honoraria; Prime Oncology: Honoraria; NIH: Research Funding; Janssen: Consultancy; Pharamcyclics: Research Funding; Raphael Pharma: Research Funding. Palomba:Merck & Co Inc.: Other: Immediate Family Member, Consultancy (includes expert testimony); Seres Therapeutics: Other: Immediate Family Member, Equity Ownership and Membership on an entity's Board of Directors or advisory committees; Hemedicus: Other: Immediate Family Member, Speakers Bureau ; Kite Pharmaceuticals: Other: Immediate Family Member, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; STRAXIMM: Other: Immediate Family Member, Membership on an entity's Board of Directors or advisory committees; Noble Insights: Consultancy; Evelo: Other: Immediate family member, Equity Ownership; MSK (IP for Juno and Seres): Other: Immediate Family Member, Patents & Royalties - describe: intellectual property rights . Rodriguez-Rivera:Memorial Sloan Kettering Cancer Center: Employment. Sauter:Juno Therapeutics: Consultancy, Research Funding; Sanofi-Genzyme: Consultancy, Research Funding; Spectrum Pharmaceuticals: Consultancy; GSK: Consultancy; Novartis: Consultancy; Genmab: Consultancy; Precision Biosciences: Consultancy; Kite/Gilead: Consultancy; Celgene: Consultancy. Straus:Seattle Genetics: Consultancy, Honoraria; Hope Funds for Cancer Research: Membership on an entity's Board of Directors or advisory committees; Elsevier (PracticeUpdate): Consultancy, Honoraria. Vardhana:ADC Therapeutics: Consultancy; Rheos Pharmaceuticals: Honoraria; Agios Pharmaceuticals: Honoraria. Younes:Roche: Consultancy, Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Curis: Honoraria, Research Funding; Merck: Honoraria, Research Funding; Abbvie: Honoraria; Takeda: Honoraria; Pharmacyclics: Research Funding; AstraZeneca: Research Funding; Genentech: Research Funding; Biopath: Consultancy; Xynomics: Consultancy; Epizyme: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; HCM: Consultancy; BMS: Research Funding; Syndax: Research Funding. Zelenetz:Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Beigene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Genentech/Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bayer: Consultancy, Membership on an entity's Board of Directors or advisory committees; MEI Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Astra-Zeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees; DAVA Oncology: Consultancy, Membership on an entity's Board of Directors or advisory committees; Verastem: Consultancy, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees; DAVA Oncology: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees; Genentech/Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees; Morphosys: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bayer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Beigene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Astra-Zeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics/AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Morphosys: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics/AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Verastem: Consultancy, Membership on an entity's Board of Directors or advisory committees; MEI Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees. Matasar:GlaxoSmithKline: Honoraria, Research Funding; Daiichi Sankyo: Consultancy; Juno Therapeutics: Consultancy; Teva: Consultancy; Rocket Medical: Consultancy, Research Funding; Seattle Genetics: Consultancy, Honoraria, Other: Travel, accomodation, expenses, Research Funding; Janssen: Honoraria, Research Funding; Bayer: Other: Travel, accommodation, expenses; Genentech, Inc.: Consultancy, Honoraria, Other: Travel, accommodation, expenses , Research Funding; Bayer: Consultancy, Honoraria, Other; Roche: Consultancy, Honoraria, Other: Travel, accommodation, expenses , Research Funding; Merck: Consultancy, Equity Ownership; Pharmacyclics: Consultancy, Honoraria, Research Funding.