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4503 CAR T Cell Therapy in Early Relapsed/Refractory Large B-Cell Lymphoma: Real World Analysis from the Cell Therapy Consortium

Program: Oral and Poster Abstracts
Session: 628. Aggressive Lymphomas: Cellular Therapies: Poster III
Hematology Disease Topics & Pathways:
Research, Lymphomas, Non-Hodgkin lymphoma, Clinical Research, Chimeric Antigen Receptor (CAR)-T Cell Therapies, Diseases, Therapy sequence, Real-world evidence, Aggressive lymphoma, Treatment Considerations, Biological therapies, Lymphoid Malignancies, Human
Monday, December 9, 2024, 6:00 PM-8:00 PM

Alexandra E. Rojek, MD1, Nausheen Ahmed, MD2, Marina Gomez Llobell, MD, MS3*, Sairah Ahmed, MD4, Marie Hu, MD5, Monica Mead, MD6, Andy Chen, MD, PhD7, Vivek Patel, MD8, Jamie Brower, MS9*, Veronika Bachanova, MD, PhD5, Richard T. Maziarz, MD7, Olalekan O. Oluwole, MD, MPH, MBBS8, Michael R Bishop, MD1,10, David L. Porter, MD9, Miguel Angel Perales, MD3, Joseph P. McGuirk, DO11, Peter A. Riedell, MD1,10 and Daniel J. Landsburg, MD9

1Department of Medicine, Section of Hematology/Oncology, University of Chicago, Chicago, IL
2University of Kansas Cancer Center, Kansas City, KS
3Cellular Therapy Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
4Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX
5Division of Hematology, Oncology, and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN
6Department of Medicine/Division of Hematology and Oncology, UCLA Medical Center, Los Angeles, CA
7Knight Cancer Institute, Oregon Health and Science University, Portland, OR
8Division of Hematology/Oncology, Vanderbilt University Medical Center, Nashville, TN
9Abramson Cancer Center, Department of Medicine, Division of Hematology-Oncology, University of Pennsylvania, Philadelphia, PA
10David and Etta Jonas Center for Cellular Therapy, University of Chicago, Chicago, IL
11Division of Hematologic Malignancies & Cellular Therapeutics, University of Kansas Medical Center, Kansas City, KS

Introduction

Anti-CD19 CAR T cell therapy with axicabtagene ciloleucel (axi-cel) and lisocabtagene maraleucel (liso-cel) was recently approved as second line (2L) therapy for patients (pts) with large B-cell lymphoma (LBCL) whose disease relapses within 12 months (mo) of completion of or is refractory to frontline therapy (early R/R). However, limited real-world data on CAR T outcomes for early R/R LBCL are available by line of therapy. We performed a retrospective multicenter study to evaluate the real-world outcomes of early R/R LBCL pts treated with CAR T in 2L as compared to the 3L+ setting.

Methods

Pts aged ≥ 18 years (yrs) with early R/R LBCL who received commercial axi-cel, tisagenlecleucel (tisa-cel), or liso-cel infusion from 4/2018 – 6/2023 at 9 academic US medical centers were identified from the Cell Therapy Consortium registry. Bridging therapy (BT) initiated prior to leukapheresis and continued until lymphodepleting chemotherapy (LDc) was not considered a separate treatment line. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were graded per ASTCT consensus criteria. Tumor response was assessed per Lugano criteria.

Results

As of 6/25/24, we identified 155 pts with early R/R disease of whom 51% had primary refractory disease. Among 53 (34%) pts receiving CAR T in 2L, 74% received axi-cel and 26% liso-cel, and among 102 (66%) pts receiving CAR T in 3L+, 48% received axi-cel, 24% tisa-cel and 28% liso-cel. Median age at leukapheresis was 63yrs (IQR: 56-70) with 26% >70yrs, 67% were male, 15% had an ECOG performance status (PS) ≥ 2, and 11% were non-Caucasian. Fludarabine/cyclophosphamide LDc was received by 76% of pts and bendamustine by 23%. Forty-seven percent of pts had elevated LDH pre-LDc, and 39% achieved an objective response to BT (complete or partial response). Baseline patient characteristics that differed between pts receiving 2L vs 3L+ CAR T were in disease status at time of referral (51% refractory in 2L vs 35% in 3L+, p<0.01), and CAR T product received (74% axi-cel in 2L vs 48% in 3L+, p<0.01).

Any grade CRS occurred in 68% of all pts (6% grade 3-4). Any grade ICANS occurred in 35% of pts (15% grade 3-4). There were no differences in rates of CRS or ICANS (no CRS/ICANS vs grade 1-2 vs 3-4) between pts receiving 2L vs 3L+ CAR T. Fifty (32%) pts died related to lymphoma. Fifteen deaths were unrelated to lymphoma with the most common causes of infection (4%), other malignancy (2%) and other causes (3%). Causes of death were similar between pts receiving 2L vs 3L+ CAR T.

Out of 137 (89%) pts evaluable at 30 days post-infusion, objective response rate (ORR) was 80% and complete response (CR) rate was 54%. Out of 122 (78%) pts evaluable at 90 days post-infusion, ORR was 70% and CR rate was 57%. There was no significant difference in either ORR or CR rate for those treated with 2L or 3L+ CAR T.

Median time of follow-up was 11.1 mo (range: 0.2-63 mo). Progression-free survival (PFS) at 9 mo was 48% (95%CI: 41-57%) for all pts. Pts treated with CAR T in 2L had a 9 mo PFS of 56% (95%CI: 44-71%) compared to 45% (95%CI: 36-56%) in 3L+ (p=0.18). Overall survival (OS) at 9 mo was 64% (95%CI: 57-72%) for all pts. Pts treated with CAR T in 2L had a 9 mo OS of 75% (95%CI: 63-88%) compared to 59% (95%CI: 50-69%) in 3L+ (p=0.11). Nine-month non-relapse mortality for all pts was 9% (95%CI: 4-13%) with no significant difference between 2L vs 3L+.

Factors included in multivariable analysis (MVA) were age at time of leukapheresis, ECOG PS, response to frontline therapy, CAR T product, elevated LDH pre-LDc, discrete number of lines of prior therapy, and response to BT. Factors associated with PFS on MVA were elevated LDH pre-LDc (HR 3.6, p<0.01) and ECOG PS (0,1,≥2) (HR 1.8, p=0.01). Factors associated with OS on MVA were elevated LDH pre-LDc (HR 2.7, p<0.01), discrete number of lines of prior therapy (HR 1.3, p<0.01), and ECOG PS (0,1, ≥2) (HR 1.9, p=0.02).

Conclusions

In this real-world analysis of pts with early R/R LBCL after frontline therapy, outcomes of pts treated with commercial CAR T in both the 2L and 3L+ setting yield favorable response and survival outcomes. While our analysis is limited by short follow-up and limited subgroup cohort size, our data suggest similar outcomes for early R/R LBCL pts treated with CAR T in 2L vs 3L+. Selection of more fit pts and efforts to reduce disease burden prior to infusion may improve survival outcomes for early R/R LBCL pts treated with CAR T regardless of line of therapy.

Disclosures: Ahmed: Kite/Gilead: Consultancy, Honoraria; Legend Biotech: Consultancy, Honoraria; BMS: Consultancy, Honoraria. Ahmed: Nektar: Research Funding; Janssen: Research Funding; Myeloid Therapeutics: Consultancy; Kite, a Gilead Company: Consultancy, Research Funding; Merck: Research Funding; Bristol Myers Squibb: Research Funding; Xencor: Research Funding; ADC Therapeutics: Consultancy. Chen: Novartis: Research Funding; BMS: Research Funding; ADC Therapeutics: Consultancy; Elsevier: Consultancy; Kite: Research Funding; Fate Therapeutics: Research Funding. Bachanova: Incyte: Research Funding; Citius: Research Funding. Maziarz: Orca: Research Funding; Kite, a Gilead Company: Consultancy, Research Funding; Incyte: Consultancy, Research Funding; Novartis: Consultancy, Other: participated in data and safety monitoring boards , Research Funding; Ori-cell Therapeutic: Honoraria; Gilead Sciences: Other: stock or other ownership; Artiva Bio: Other: Leadership Role; stock or other ownership; Athersys: Other: participated in data and safety monitoring boards, Patents & Royalties; Bristol Myers Squibb: Consultancy, Research Funding; CRISPR Therapeutics: Consultancy; Autolus: Consultancy; Vor BioPharma: Other: participated in data and safety monitoring boards; Century Therapeutics: Other: participated in data and safety monitoring boards. Oluwole: Daichi Sankyo: Research Funding; TGR: Consultancy; Novartis: Consultancy; Nektar: Consultancy; Kite, a Gilead Company: Consultancy, Research Funding, Speakers Bureau; Epizyme: Consultancy; Caribou Biosciences: Consultancy; ADC: Consultancy, Speakers Bureau; Pfizer: Consultancy, Honoraria, Research Funding; Allogene: Research Funding; Gilead Sciences: Consultancy, Honoraria; AbbVie: Consultancy; Cargo: Consultancy; Bioheng: Consultancy. Bishop: ADC Therapeutics: Honoraria, Speakers Bureau; GenMab: Honoraria, Speakers Bureau; AstraZeneca: Honoraria, Speakers Bureau; Iovance Biotherapeutics: Consultancy; Sana Biotechnology: Consultancy, Honoraria; In8bio: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Galapagos: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Achieve Clinics, In8Bio: Current holder of stock options in a privately-held company; Achieve Clinics, Arcellx, Autolus, BMS, Chimeric Therapeutics, CRISPR Therapeutics, In8Bio, Iovance Biotherapeutics, Kite-Gilead, Optum Health, Novartis, Sana Biotechnology: Consultancy; Bristol-Meyer-Squibb: Consultancy, Honoraria, Speakers Bureau; Chimeric Therapeutics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; CRISPR Therapeutics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Kite/Gilead: Consultancy, Honoraria, Research Funding, Speakers Bureau; Servier: Consultancy, Honoraria, Speakers Bureau; Incyte: Honoraria; Arcellx, Autolus, Bristol-Myers Squibb, CRISPR Therapeutics, Lyell, Gilead Sciences and Novartis: Research Funding; AbbVie, ADC Therapeutics, Bristol-Myers Squibb, Gilead Sciences, Incyte, Novartis, Sanofi and Servier: Honoraria, Speakers Bureau. Porter: Mirror Biologics: Consultancy; Tmunity.: Patents & Royalties; Novartis: Patents & Royalties, Research Funding; BMS: Research Funding; Novartis: Consultancy; Genentech: Current equity holder in publicly-traded company; Roche: Current equity holder in publicly-traded company; Janssen (Johnson and Johnson): Consultancy; Sana Biotechnology: Consultancy; Angiocrine: Consultancy; Kite/Gilead: Consultancy; Verismo Therapeutics. Research Funding: Novartis; BMS: Consultancy. Perales: AbbVie: Honoraria; OrcaBio: Consultancy, Current holder of stock options in a privately-held company; Sellas: Other: DSMB member; Celgene: Consultancy, Honoraria; Syncopation: Consultancy; Cidara Therapeutics: Other: DSMB member; Caribou Biosciences: Consultancy; Merck: Consultancy, Research Funding; Allovir: Consultancy; Allogene: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria; Kite/Gilead: Consultancy, Honoraria, Research Funding; Incyte: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Omeros: Consultancy, Current equity holder in publicly-traded company; Miltenyi Biotec: Consultancy, Honoraria, Research Funding; Nektar Therapeutics: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy; VectivBio AG: Consultancy, Research Funding; Adicet: Consultancy; Vor Biopharma: Consultancy; Astellas: Honoraria; Karyopharm: Honoraria; MorphoSys: Honoraria; Takeda: Honoraria; Medigene: Other: DSMB member; Servier: Other: DSMB member. McGuirk: Sana technologies: Consultancy; Legend biotech: Consultancy; CRISPR therapeutics: Consultancy; Caribou bio: Consultancy; NEKTAR therapeutics: Consultancy; Autolus: Consultancy; Allo Vir: Consultancy; Envision: Consultancy; Kite: Consultancy; Novartis: Consultancy; BMS: Consultancy. Riedell: Nektar Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Fate Therapeutics: Research Funding; Intellia Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; ADC Therapeutics: 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; Genentech/Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Tessa Therapeutics: Research Funding; Cargo Therapeutics: Research Funding; Calibr: Research Funding; CRISPR Therapeutics: Research Funding; CVS Caremark: Consultancy, Membership on an entity's Board of Directors or advisory committees; Xencor: Research Funding; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Genmab: Consultancy, Membership on an entity's Board of Directors or advisory committees; Kite/Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Cellectis: Research Funding; Sana Biotechnology: 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; Adaptive Biotechnologies: Honoraria. Landsburg: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; GenMab: Honoraria; Calithera: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; ADC Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

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