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3751 Outcomes of Chimeric Antigen Receptor (CAR) T-Cell Therapy in Extranodal (EN) B-Cell Non-Hodgkin Lymphoma (NHL): Results from a Multicenter Analysis

Program: Oral and Poster Abstracts
Session: 906. Outcomes Research: Lymphoid Malignancies Excluding Plasma Cell Disorders: Poster II
Hematology Disease Topics & Pathways:
Research, Adult, Lymphomas, Non-Hodgkin lymphoma, Clinical Research, Diseases, Real-world evidence, Lymphoid Malignancies, Human
Sunday, December 8, 2024, 6:00 PM-8:00 PM

Frederique St-Pierre, MD1, Subodh Bhatta, PHD2, Peter Doukas, MD3*, Madeline A. Jenkin, BS4*, Kaitlin Annunzio, DO5, Alexandra E. Rojek, MD6, Yun Kyoung Tiger, MD, PhD7, Brittany McCall, MD8*, Khaled Alhamad, MD9*, Alec Hansen10*, Juan Pablo Alderuccio, MD11, Olutobi Adewale, MD12*, Keem Patel, MD12*, Asaad Trabolsi, MD13, Izidore S. Lossos, MD14, Lindsey Fitzgerald, MD15, Thomas Ollila, MD16, Matthew Matasar, MD, MS17, Justin Kline, MD18, Reem Karmali, MD19 and Narendranath Epperla, MD, MS9

1Department of Hematology/Oncology, Great River Health/Southeast Iowa Regional Medical Center, Burlington, IA
2Department of Medicine, Division of Hematology, The Ohio State University, Columbus, OH
3Division of Hematology/Oncology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL
4Northwestern University Feinberg School of Medicine, Chicago
5The James Cancer Center, The Ohio State University Wexner Medical Center, Columbus, OH
6Department of Medicine, Section of Hematology/Oncology, University of Chicago, Chicago, IL
7Division of Hematology, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ
8Division of Hematology-Oncology, Rhode Island Hospital, Providence, RI
9Division of Hematology and Hematologic Malignancies, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT
10Huntsman Cancer Institute, The University of Utah, Salt Lake City, UT
11Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL
12Department of Hematology, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ
13University of Miami, Sylvester Comprehensive Cancer Center, Miami, FL
14Division of Hematology, Sylvester Comprehensive Cancer Center, Miami, FL
15Huntsman Cancer Institute, University of Utah, Salt Lake City, UT
16Lifespan Cancer Institute, Rhode Island Hospital, Providence, RI
17Division of Blood Disorders, Rutgers Cancer Institute of New Jersey and RWJBarnabas Health, New York, NY
18University of Chicago, Chicago, IL
19Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL

Introduction: EN lymphoma is defined by involvement of sites outside of the lymph nodes, spleen, thymus and oropharyngeal lymphoid tissue. Certain EN sites are associated with a worse prognosis in diffuse large B-cell lymphoma (DLBCL) (Castillo et al. AJH 2014). Although CAR-T has become standard in treating patients (pts) with relapsed/refractory (R/R) LBCL, the outcomes of CAR-T in pts with EN disease are not well established.

Methods: We performed a retrospective multi-center analysis of pts with R/R aggressive B-cell NHL who had EN disease and received treatment with anti-CD19 CAR-T. EN disease could be present at diagnosis and/or at time of CAR-T. The primary objective was to determine the overall survival (OS), while secondary objectives included overall and complete response rates (ORR/CRR), progression free survival (PFS), and CAR-T toxicities. Survival outcomes were estimated using the Kaplan-Meier method and compared between groups using the log-rank test.

Results: 282 pts from 7 institutions were included in the analysis. Median age at diagnosis was 60 years (range:18-85), with a 3:2 male to female ratio. 60% (n=169) of pts had DLBCL histology, 14% (n=40) had high-grade B-cell lymphoma, 15% (n=43) had transformed indolent lymphoma, and 5% had follicular lymphoma. 42% (85 of 201 available) of pts had primary refractory disease. Median number of prior lines of therapy was 3 (range:0-9). 53% (n=150) of pts received bridging therapy prior to CAR-T. 99% (278 of 281 available) of pts received a commercial CD19 CAR (43% axicabtagene ciloleucel, 30% tisagenlecleucel, 25% lisocabtagene maraleucel, 2% brexucabtagene autoleucel), while the remaining 1% (n=3) received a bispecific or allogeneic CAR. Median follow up time was 3 years (range:0.08-7).

Median OS was 2.41 [95% CI: 1.52, 4.3] years from the day of CAR-T infusion. Survival outcomes were similar between pts with primary EN disease (i.e. the lymphoma originated in an EN site) vs secondary EN disease. Presence of EN disease at CAR-T did not predict survival (p=0.23). 13% (26 of 204 available) of pts did not have EN disease at diagnosis, but later developed EN disease at time of CAR-T. These pts had poorer survival, with median OS 0.91 [95% CI: 0.41, Not Reached (NR)] vs 3.03 [95% CI: 2.14, NR] years for patients with EN disease at diagnosis (p=0.027). Baseline characteristics were similar between the two groups including age, prior lines of therapy, cell-of-origin, and MYC alterations. Other factors associated with poorer outcomes included use of bridging therapy with median OS 1.33 [95% CI: 0.97. 2.14] vs 5.41 [95% CI: 2.84, NR] years for pts who did not receive bridging (p≤0.01), and refractory disease at time of CAR-T with median OS 1.54 [95% CI: 1.10, 2.84] vs NR [95% CI: 5.41, NR] for patients without refractory disease (p≤0.01).

Median PFS was 0.48 [95% CI: 0.30, 0.85] years, 1-year PFS was 41% [95% CI: 35, 47] and 3-year PFS was 33% [95% CI: 28, 39]. ORR was 65% [95% CI: 59, 71] and CRR was 42% [95% CI: 36, 48] at first response assessment. Cytokine release syndrome (CRS) and neurotoxicity occurred in 73% (205 of 281 available) and 38% (108 of 281 available) of pts, respectively. Rates of grade ≥ 3 of CRS and neurotoxicity were 6% (n=17) and 19% (n=54), respectively. Median durations of CRS and neurotoxicity were 3 days (range:0-57) and 5 days (range:0-188), respectively. Transfusion support (PRBC and platelets) and filgrastim beyond the first 30 days post CAR-T was needed in 18% (50 of 272 available), 20% (54 of 272 available), and 34% (93 of 272 available) of pts, respectively. Secondary malignancy occurred in 2% (5 of 204 available) of pts, including one case of T-cell large granular lymphocytic leukemia.

Conclusion:

In this large multi-center cohort study of EN LBCL undergoing CAR-T, we found no significant difference in OS based on the presence or absence of EN disease at CAR-T or whether it was primary or secondary EN lymphoma. Pts without EN disease at diagnosis who later developed EN disease at time of CAR-T had worse OS. OS, PFS, and rate of grade 3 CRS and neurotoxicity in our study (EN B-cell NHL) were comparable to the real-world outcomes of CAR-T in R/R LBCL (Jacobson et al. TCT 2024). Further analysis including comparison of single-site versus multi-site EN disease as well as multivariate analysis of factors with significant impact on survival is ongoing.

Disclosures: Alderuccio: Genmab: Research Funding; AbbVie: Consultancy; ADC Therapeutics: Consultancy, Research Funding; Regeneron: Consultancy; Genentech: Consultancy; BeiGene: Research Funding. Lossos: Not specified: Patents & Royalties; ADCT: Research Funding; University of Miami: Current Employment. Ollila: Lilly: Research Funding; Ono Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Research Funding; ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees. Matasar: Kite: Honoraria; Immunovaccine Technologies: Research Funding; IMV Therapeutics: Honoraria; Takeda: Honoraria; Roche: Consultancy, Honoraria, Research Funding; GM Biosciences: Consultancy, Research Funding; Genmab: Membership on an entity's Board of Directors or advisory committees; Johnson & Johnson: Consultancy, Honoraria, Research Funding; Epizyme: Honoraria; Pfizer: Honoraria; Regeneron Pharmaceuticals, Inc.: Honoraria; Genentech: Consultancy, Honoraria, Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; Pharmacyclics: Consultancy, Honoraria, Research Funding; ADC Therapeutics: Honoraria; AstraZeneca: Honoraria; BMS/Celgene: Honoraria; Allogene: Membership on an entity's Board of Directors or advisory committees; Merck: Current equity holder in publicly-traded company; Bayer: Consultancy, Honoraria, Research Funding. Kline: Curio Science: Honoraria; Merck: Research Funding; Gilead Sciences: Consultancy; BMS: Consultancy; BeiGene: Consultancy; Abbvie: Consultancy; Genmab: Consultancy; Seagen: Consultancy; Targeted Oncology: Honoraria. Karmali: Genentech/Roche: Honoraria; Abbvie: Honoraria; BMS: Honoraria; Incyte: Speakers Bureau; AstraZeneca: Speakers Bureau; BeiGene: Speakers Bureau; Ipsen: Speakers Bureau; Genmab: Honoraria. Epperla: Ispen: Other: Advisory Board; Genetech: Speakers Bureau; Novartis: Consultancy; Lilly: Other: Advisory Board; Beigene: Speakers Bureau.

*signifies non-member of ASH