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2377 Evaluation of Outcomes and Toxicities of Commercial Axicabtagene Ciloleucel (axi-cel) and Tisagenlecleucel (tisa-cel) for Relapsed or Refractory (R/R) Follicular Lymphoma (FL): Real-World Evidence (RWE) from 10 US Academic Centers

Program: Oral and Poster Abstracts
Session: 906. Outcomes Research: Lymphoid Malignancies Excluding Plasma Cell Disorders: Poster I
Hematology Disease Topics & Pathways:
Research, Lymphomas, Clinical Research, Chimeric Antigen Receptor (CAR)-T Cell Therapies, Indolent lymphoma, Diseases, Real-world evidence, Treatment Considerations, Biological therapies, Lymphoid Malignancies
Saturday, December 7, 2024, 5:30 PM-7:30 PM

John Sharp, MD1, Paolo Strati, MD2, Subodh Bhatta, PhD3, Jennifer J. Huang, MD, PhD4, Colin Thomas, MD5, Daniel K Reef, MD6, Alexander Gorzewski7*, Catherine Reinert8*, Andinet Teferra9*, Ari Pelcovits, MD10, Thomas Ollila, MD11, Joseph E. Maakaron, MD12, Manali K. Kamdar, MD13, Lindsey Fitzgerald, MD14, Reem Karmali, MD15, Natalie Grover, MD16, Stefan K. Barta, MD17, Timothy Voorhees, MD, MSc18, Mazyar Shadman, MD, MPH19, Sairah Ahmed, MD2 and Narendranath Epperla, MD, MS20

1James Comprehensive Cancer Center, The Ohio State University, Columbus, OH
2Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX
3The Ohio State University, Columbus, OH
4Fred Hutchinson Cancer Center, Seattle, WA
5Thomas Jefferson University Hospital, Philadelphia, PA
6Department of Medicine, Division of Oncology, University of North Carolina-Chapel Hill, Chapel Hill, NC
7Northwestern University, Chicago
8University of Colorado Cancer Center, Aurora, CO
9Division of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, MN
10Rhode Island Hospital, Providence, RI
11Brown University, Providence, RI
12Division of Hematology, Oncology, and Transplantation, University of Minnesota Medical Center, Minneapolis, MN
13University of Colorado, Denver, CO
14Huntsman Cancer Institute, University of Utah, Salt Lake City, UT
15Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL
16University of North Carolina, Chapel Hill, NC
17Abramson Cancer Center, The Fox Chase Cancer Center Foundation, Philadelphia, PA
18Division of Hematology, The Ohio State University, Columbus, OH
19Fred Hutchinson Cancer Research Center, Seattle, WA
20Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University, Columbus, OH

Background: The advent of chimeric antigen receptor T-cell (CAR-T) therapy revolutionized the treatment landscape in R/R FL, including those with progression of disease within 24 months (POD24). However, RWE describing outcomes for patients with R/R FL treated with CAR-T is lacking. Hence, we sought to evaluate outcomes and toxicities of axi-cel vs tisa-cel in R/R FL from 10 US academic centers.

Methods: This is a multi-center retrospective cohort study of patients (pts) with R/R FL who received commercial CAR-T with axi-cel or tisa-cel between 2021 and 2024. Pts with biopsy-proven transformed lymphoma were excluded. Endpoints included day +90 overall response rate (ORR) and complete response rate (CRR), progression-free survival (PFS), overall survival (OS) and rates of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). ORR was defined as partial response (PR) rate + CRR according to Lugano criteria. PFS was calculated from CAR-T infusion to progression or death, censoring those alive without progression at last contact, and OS was calculated from CAR-T infusion to death, censoring those alive at last contact. CRS and ICANS were graded according to American Society for Transplantation and Cellular Therapy criteria. Kaplan-Meier method was used to estimate survival functions with log-rank test to compare groups. Cox regression was done to identify prognostic factors for PFS and OS.

Results: A total of 111 pts were included. Among these, 91 (82%) received axi-cel and 20 (18%) received tisa-cel. Pts receiving tisa-cel were older (median age, 74 yrs [range: 29-82] vs 60 yrs [range: 38-82], p<0.001) with female predominance (60% vs 23%, p=0.003), and were more likely to receive bendamustine lymphodepletion (35% vs 3%, p<0.001) compared to those receiving axi-cel. Otherwise, groups were similar between axi-cel and tisa-cel with regards to race (white 86% vs 85%, black 6% vs 5%, p=1.0), Eastern Cooperative Oncology Group performance status (0-1 96% vs 100%, ≥2 4% vs 0%, p=1.0), stage at diagnosis (I-II 20% vs 13%, III 29% vs 25%, IV 52% vs 63%, p=0.82), bulky disease at diagnosis (44% vs 53%, p=0.71), primary refractory disease (24% vs 16%, p=0.56), POD24 (62% vs 56%, p=0.83), median prior lines of therapies (3 [range: 3-12] vs 3 [range: 2-5], p=0.57), receipt of bridging therapy (43% vs 65%, p=0.12), disease status immediately prior to CAR-T (CR/PR 21% vs 16%, stable disease 18% vs 16%, progressive disease (61% vs 68%, p=1.0), and pre-lymphodepletion lab values.

The median follow up was 1.3 yrs (range: 0.9 - 3). Day +90 ORR and CRR were comparable between axi-cel and tisa-cel (ORR 89% [95% CI: 80, 95] vs 83% [95% CI: 57, 96], p=0.43, CRR 85% [95% CI: 76, 92] vs 71% [95% CI: 44, 90], p=0.16). Median PFS was significantly longer with axi-cel vs tisa-cel (not reached (NR) [95% CI: 24.6 months, NR] vs 9.1 months [95% CI: 7.4 months, NR], p=0.003) with 1 yr PFS estimates of 71% (95% CI: 61, 82) vs 31% (95% CI: 14, 68), respectively. Median OS was NR in both groups (95% CI: NR, NR for both) with 1 yr OS estimates of 90% (95% CI: 83, 97) in axi-cel vs 87% (95% CI: 72, 100, p=0.32) in tisa-cel.

There was no difference in frequency of any grade CRS (78% vs 70%, p=0.56) or grade ≥3 CRS (6% vs 5%, p=1.0) between axi-cel vs tisa-cel. Rates of any grade (43% vs 20%, p=0.10) and grade ≥3 ICANS (20% vs 5%, p=0.19) were numerically higher with axi-cel vs tisa-cel. Notably, more patients received tisa-cel in the outpatient setting (40% vs 9%, p=0.002). Among patients receiving outpatient CAR-T, frequencies of unexpected hospitalizations within 30 days between axi-cel (6 of 8 pts) and tisa-cel (5 of 8 pts) were comparable (p=1.0). Among patients receiving inpatient CAR-T, frequency of re-admissions within 30 days between axi-cel (20 of 83 pts) and tisa-cel (1 of 12 pts) were comparable (p=0.29). In Cox model, receipt of tisa-cel (vs axi-cel) and POD24 were associated with inferior PFS (HR 4.6, 95% CI: 1.5, 13.7, p=0.007, HR 5.03, 95% CI: 2.0,12.9, p<0.001, respectively). No variables were prognostic for OS.

Discussion: This is the first RWE analyzing outcomes and toxicities of axi-cel and tisa-cel in R/R FL. ORR and CRR were comparable between the two CAR-T products. Rates of any and grade ≥3 ICANS were numerically higher with axi-cel, though this did not reach statistical significance. PFS was significantly inferior for recipients of tisa-cel compared to axi-cel with the caveat that the tisa-cel group was relatively small.

Disclosures: Strati: TG Therapeutics: Consultancy; Roche-Genentech: Consultancy; Hutchison MediPharma: Consultancy; Ipsen: Consultancy; ALX Oncology: Research Funding; Kite, a Gilead company: Consultancy, Research Funding; Sobi ADC Therapeutics: Consultancy, Other: Travel, accommodations, expenses, Research Funding; Acerta-Astrazeneca: Consultancy, Research Funding; Abbvie-Genmab: Consultancy. Reef: Regeneron Pharmaceuticals: Current equity holder in publicly-traded company. Ollila: Ono Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Research Funding; Lilly: Research Funding; ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees. Maakaron: Gilead: Research Funding; Atara: Research Funding; CRISPR: Research Funding; Precision Biosciences: Research Funding; Scripps Research Institute: Research Funding; VOR Bio: Research Funding; Affimed: Research Funding. Kamdar: SeaGen: Speakers Bureau; Celgene: Other: Data Monitoring Committee; Genentech: Other: Data Monitoring Committee; Celgene/Bristol-Myers Squibb: Consultancy; Beigene: Consultancy; AstraZeneca: Consultancy; AbbVie: Consultancy; Genentech: Consultancy; Novartis: Research Funding. Karmali: AstraZeneca: Speakers Bureau; Ipsen: Speakers Bureau; BeiGene: Speakers Bureau; Abbvie: Honoraria; BMS: Honoraria; Incyte: Speakers Bureau; Genmab: Honoraria; Genentech/Roche: Honoraria. Grover: Kite: Honoraria; Sangamo: Current holder of stock options in a privately-held company; Janssen: Honoraria; Cabaletta: Research Funding; Genentech: Honoraria; Ono Pharma: Honoraria; Caribou: Honoraria; BMS: Honoraria, Research Funding; ADC Therapeutics: Honoraria; Regeneron: Honoraria, Research Funding; Novartis: Honoraria; Seagen: Honoraria. Barta: Janssen: Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Consultancy; Kyowa Kirin: Consultancy; BMS: Consultancy; Acrotech: Consultancy. Voorhees: Genmab: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy; Kite: Research Funding; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Recordati: Consultancy, Research Funding; Incyte/Morphosys: Research Funding; Viracta: Research Funding. Shadman: Merck: Consultancy; Genentech: Consultancy, Research Funding; AstraZeneca: Consultancy, Research Funding; Genmab: Consultancy, Research Funding; Kite Pharma: Consultancy; Morphosys/Incyte: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy; BeiGene: Consultancy, Research Funding; Janssen: Consultancy; Fate therapeutics: Consultancy; Nurix: Consultancy; Eli Lilly: Consultancy; Mustang Bio: Research Funding; Vincerx: Research Funding; Koi Biotherapeutics: Current holder of stock options in a privately-held company; Bristol Myers Squibb (spouse): Current Employment; AbbVie: Consultancy, Research Funding. Ahmed: Merck: Research Funding; Janssen: Research Funding; Kite, a Gilead Company: Consultancy, Research Funding; Myeloid Therapeutics: Consultancy; Nektar: Research Funding; Bristol Myers Squibb: Research Funding; Xencor: Research Funding; ADC Therapeutics: Consultancy. Epperla: Lilly: Other: Advisory Board; Novartis: Consultancy; Beigene: Speakers Bureau; Ispen: Other: Advisory Board; Genetech: Speakers Bureau.

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