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4886 Second Vs Third Line Treatment with Axicabtagene Ciloleucel for Large B Cell Lymphoma – a Real-Life National Multicenter Retrospective Cohort Study with Propensity Score Matching

Program: Oral and Poster Abstracts
Session: 705. Cellular Immunotherapies: Late Phase and Commercially Available Therapies: Poster III
Hematology Disease Topics & Pathways:
Research, Biological therapies, adult, Lymphomas, Clinical Research, B Cell lymphoma, Chimeric Antigen Receptor (CAR)-T Cell Therapies, Diseases, real-world evidence, Therapies, clinical procedures, Lymphoid Malignancies, Technology and Procedures, Study Population, Human
Monday, December 11, 2023, 6:00 PM-8:00 PM

Gil Fridberg1*, Odelia Amit, MD1*, Liat Shargian, MD2*, Ofrat Beyar Katz3, Sigal Grisariu, MD4*, Chava Perry, MD1*, Ronit Gurion, MD5*, Batia Avni, MD4*, Tsila Zuckerman3*, Irit Avivi Mazza, MD1* and Ron Ram, MD1

1BMT Unit, Tel Aviv Sourasky Medical Center and Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
2Hematology Institute, Davidoff Center, Rabin Medical Center, and Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
3Department of Hematology and BMT, Rambam Health Care Campus, Haifa, Israel
4Bone Marrow Transplantation & Cancer Immunotherapy Department, Hadassah-Hebrew University Medical Center and Faculty of Medicine, the Hebrew University of Jerusalem, Jerusalem, Israel
5Institute of Hematology, Davidoff Cancer Center, Rabin Medical Center, Petah Tikva, Israel

Background: Superiority of Axicabtagene Ciloleucel (Axi-Cel) in relapsed/refractory (R/R) large B cell lymphomas (LBCL) compared with standard of care was shown in both the 3rd and 2nd line setting. However, optimal timing for incorporation of CAR-T is not well established. We aimed to compare efficacy, toxicity profile, and product kinetics of Axi-Cel as 2nd vs 3rd line of treatment. Methods: we performed a national real world retrospective study of consecutive patients treated with Axi-Cel as 2nd line with propensity score-matched patients treated with 3rd line treatment. Patients were matched for age (±2 years), Eastern Cooperative Oncology Group (ECOG) performance status, and disease status at lymphodepletion. Disease status and response were defined by the Lugano criteria, cytokine release syndrome (CRS) and immune effector cells-associated neurotoxicity syndrome (ICANS) were defined by ASTCT Consensus (2019) and progression-free survival (PFS) was calculated from infusion to index event. Immunophenotyping from peripheral blood at day 7+ was used to analyze expansion of CAR-T cells. Results: Between 01/2019 and 06/2023, 44 patients treated with Axi-Cel fulfilled the inclusion criteria, 22 in each cohort. Groups were well matched in the propensity score domains (mean difference 2, p=.65 for age, mean square .32, p=.57 for ECOG, and mean square .26, p=.61 for disease status at lymphodepletion). Median follow up was 2.2 (range, 1-28.8) months in 2nd line group and 10.8 (range, 1-39) months in the 3rd group. Median age was 68 (range, 39 – 84) and 66 (range, 32 – 80) years in the 2nd and 3rd line groups, respectively. There were no differences between gender (p=.76), LBCL subtypes (p=.16), % of patients receiving bridging therapy (p=.55), % of patients with elevated LDH levels prior to lymphodepletion (p=.98), and n days from collection to treatment (p=.29) between the 2 groups. There was a lower % of patients with primary refractory disease in the 2nd, compared to 3rd line therapy group (63% vs. 36%, respectively, p=.09) and a higher % of patients with transformed disease (42% vs. 14%, respectively, p=.04). Both overall and grade 3-4 incidences of CRS were similar between the 2nd line and the 3rd line groups (86% vs. 95%, p=.16 and 18% in both groups, p=1, respectively). Median days to CRS onset was also similar (1, range 0 – 5 and 2, range 0 – 7, p=.1, respectively). Both overall and grade 3-4 incidences of ICANS) were similar between the 2nd line and the 3rd line groups (41% vs. 64%, p=.48 and 14% vs. 18%, p=.73, respectively. Median days to ICANS onset was lower in the 2nd line compared to the 3rd line group (4, range 0 – 8 and 6, range 0 – 7, p=.06, respectively). There were no differences between the groups in the median tocilizumab doses (p=.21), % of patients receiving steroids (p=.12), cumulative steroids dose (p=.17), % of patients receiving growth factors (p=1), and duration of admission (p=.51). Median day +7 CAR-T blood levels were higher in the 2nd line compared to the 3rd line group (126 (range,1–791) vs. 18.1 (range, 0–988) cells/microL, p=.05, respectively). 1-month overall response rate (ORR) was 86% (CR=77%) in the 2nd line group vs 64% (CR=45%), in the 3rd line group, p=.081 Figure 1a. Three-months progression-free survival was 88% (95%, CI 64%-100%) vs. 59% (45%-73%), respectively, Figure 1b. Cox regression identified 2nd line treatment associated with better progression-free survival (HR=.15, p=.007) and progressive disease at lymphodepletion associated with worse progression-free (HR=8.5, p=.007), while age, gender, and ECOG performance status did not impact progression. Conclusions: This matched comparison showed favorable ORR and PFS rates when Axi-Cel is utilized as a 2nd line treatment vs 3rd line. Toxicity profile is similar. Higher CAR-T expansion in the 2nd line might provide insight regarding product quality and exhaustion phenotype when manufactured earlier in the LBCL treatment course. A longer follow-up is needed to test whether these findings translate to durable remission and cure.

Disclosures: Gurion: Novartis: Honoraria; Roche: Honoraria; Abbvie: Honoraria; Gilhead: Honoraria; Takeda: Honoraria; Medison: Honoraria. Avivi Mazza: AbbVie: Honoraria. Ram: Novartis: Honoraria, Research Funding; Gilead: Honoraria; MSD: Honoraria; BMS, Takeda, Sanofi, Pfizer: Honoraria.

*signifies non-member of ASH