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1944 Impact of Absolute Lymphocyte Count at Pre-Apheresis and Pre-Lymphodepletion on Chimeric Antigen Receptor (CAR)-T Therapy Outcomes in Relapsed Refractory Multiple Myeloma (RRMM)

Program: Oral and Poster Abstracts
Session: 653. Multiple Myeloma: Clinical and Epidemiological: Poster I
Hematology Disease Topics & Pathways:
Research, Clinical Research, Real-world evidence
Saturday, December 7, 2024, 5:30 PM-7:30 PM

Noriko Nishimura, MD1,2,3, Sham Mailankody, MD, MBBS2, Samantha Brown4*, Sean M. Devlin, PhD4*, Bruno Almeida Costa, MD5, Tasmin Farzana, MPH2*, Eric M Jurgens, MD2, Ross S Firestone, MD, PhD2, Karthik Nath6*, David J. Chung, MD, PhD7, Heather J. Landau, MD8, Michael Scordo, MD9, Gunjan L. Shah, MD8, Roni Shouval, MD, PhD10, Hamza Sloan Hashmi, MD2*, Hani Hassoun, MD2, Kylee H Maclachlan, PhD, BSc, FRACP, FRCPA2, Malin Hultcrantz, MD2, Neha Korde, MD2, Alexander M. Lesokhin, MD11, Urvi A. Shah, MD2, Carlyn Rose Tan, MD2, Sergio A. Giralt, MD12, Saad Z. Usmani, MD2 and Sridevi Rajeeve, MD13*

1Department of Hematology/Oncology, The Cancer Institute Hospital, Tokyo, NY, Japan
2Myeloma Service, Division of Hematologic Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
3Division of Hematologic Malignancies, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
4Department of Biostatistics and Epidemiology, Memorial Sloan Kettering Cancer Center, New York, NY
5The Mount Sinai Hospital, Brookdale Department of Geriatrics and Palliative Medicine, Icahn School of Medicine at Mount Sinai, NEW YORK, NY
6Icon Cancer Centr, South Brisbane, AUS
7Transplant and Cellular Therapy Services, Division of Hematologic Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
8Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
9Transplant and Cellular Therapy Services, Division of Hematologic Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York City, NY
10Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
11Myeloma & Cell Therapy Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
12Adult Bone Marrow Transplantation Service, Memorial Sloan Kettering Cancer Center, New York, NY
13Myeloma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY

Introduction/Background:

Chimeric antigen receptor (CAR)–modified T cells targeting BCMA have shown high response rates and durable remissions in patients with relapsed or refractory multiple myeloma (RRMM). Since this innovative therapy leverages the patient's own immune system, T cell fitness prior to CAR-T therapy is increasingly important. Acceptable thresholds for absolute lymphocyte count prior to apheresis which have prognostic impact are not clearly defined. This real-world analysis investigated pre-apheresis (A) and pre-lymphodepletion (LD) ALC, and the ALC reduction between A and LD, on survival outcomes post CAR-T for RRMM.

Methods:

This was a single center, retrospective analysis of patients with RRMM who received commercial BCMA-directed CAR-T cell therapy, ciltacabtagene autoleucel (cilta-cel) and idecabtagene vicleucel (ide-cel) between August 2021 and May 2023. We assessed the impact of Pre-A and Pre-LD ALC as well as the reduction in ALC (measured as the difference between pre-LD and pre-A ALC) on the progression-free survival (PFS) and overall survival (OS) using the Cox proportional hazard models.

Result:

Of the 54 patients included, 63% (n=34) received ide-cel and 38% (n=20) received cilta-cel. The median age was 65 years (range, 41-86) and 61% were male. Revised international staging system (R-ISS) stages I/ II/ III were 24% /41% /13%, respectively. 49% (n=26) had extramedullary disease (EMD) present and 56% (n=30) had at least 1 high-risk cytogenetic abnormality by FISH. Patients received a median of 8 (range, 1–20) prior lines of therapy, and 72% (n=38) received bridging therapy. 38% (n=20) had penta-refractory disease. The median pre-A and pre-LD ALC was 0.8×109/L (range, 0.1–2.2) and 0.8×109/L (range, 0.1–3.1), respectively. The median absolute reduction in ALC was 0.1×109/L (range, -2.8–1.0). Using the lowest quartiles as cutoffs, we defined low pre-A ALC as ≤ 0.5 ×109/L, while a high reduction between pre-A and pre-LD ALC was defined as ≥ 0.1 ×109/L based on the highest quartiles. Compared to patients with high pre-A ALC, those with low pre-A ALC received more bridging therapy (87% vs. 66%) and had a higher incidence of high-risk cytogenetics (73% vs. 49%). In contrast, patients with low and high pre-LD ALC were more balanced in terms of bridging therapy (76% vs. 69%) and high-risk cytogenetics (both 56%).

The median follow-up time from CAR-T infusion was 18months. Low pre-A ALC was associated with significantly inferior PFS in univariable analysis (HR 2.09, 95% CI 1.04–4.19, p=0.038); this difference remained significant in multivariable analysis (HR 2.10, 95% CI 1.02–4.31, p=0.044) along with 1p deletion (HR 2.54, 95% CI 1.07–6.02, p=0.034) and EMD (HR 2.51, 95% CI 1.19–5.30, p=0.015). Additionally, low pre-A ALC was significantly associated with inferior OS in univariable analysis (HR 6.40, 95% CI 2.48–16.5, p<0.001), and remained a poor prognostic factor for OS in multivariable analysis (HR 6.59, 95% CI 2.44–18.8, p<0.001) along with EMD (HR 4.31, 95% CI 1.28–14.5, p=0.018). Neither pre-LD ALC nor a high absolute reduction in ALC showed significant differences in PFS, while pre-LD ALC was significantly associated with worse OS only in the univariable setting without significance in multivariable analysis. No correlation was observed between pre-A ALC and rates of cytokine release syndrome (CRS) and Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), however, CRS was significantly more frequently noted in patients with low pre-LD ALC.

Conclusion:

In this small real-world analysis, results suggest that the pre-apheresis ALC <0.5 ×109/L may be an independent poor prognostic factor on PFS and OS in RRMM treated with CAR-T cell therapy and low pre-LD ALC may predict higher incidence of CRS after CAR-T infusion. Further investigation is warranted to determine the optimal timing of apheresis in patients with low pre-ALC in a larger cohort.

Disclosures: Mailankody: BMS, J&J, GSK, Springworks Therapeutics: Research Funding. Landau: Abbvie, Immix Biopharma, Legend Biotech, Alexion, Prothena: Consultancy; Nexcella, Janssen, Alexion, Protego, Prothena: Research Funding. Scordo: MJH Life Sciences (Cancer Network): Honoraria; Sanofi: Research Funding; Medscape: Honoraria; Angiocrine Biosciences, Inc.: Research Funding; Amgen: Research Funding; Kite - A Gilead Company: Consultancy; IDEOlogy: Honoraria; Miltenyi Biotec: Consultancy; Omeros Corporation: Consultancy, Research Funding. Shah: Janssen, Amgen, Beyond Spring, BMS, GPCR, DSMB with ArcellX.: Research Funding. Hashmi: Amgen: Consultancy; Janssen: Consultancy; Karyopharm: Consultancy. Hassoun: Janssen, Takeda: Research Funding. Hultcrantz: Abbvie, GlaxoSmithKline, SpringWorks Therapeutics, Daiichi Sankyo, Cosette Pharmaceuticals: Research Funding; Curio Science LLC, Intellisphere LLC, Janssen, Bristol Myers Squibb, and GlaxoSmithKline: Consultancy, Honoraria. Korde: Amgen, Janssen, Epizyme, and AbbVie: Research Funding; CCO, OncLive, and Intellisphere: Consultancy; Remedy Health 8/2022: Other: part of (Patient Power); Janssen: Membership on an entity's Board of Directors or advisory committees. Lesokhin: Serametrix, Inc.: Patents & Royalties; Arcellx: Consultancy, Honoraria; Memorial Sloan Kettering Cancer Center: Current Employment; F. Hoffmann-La Roche Ltd, Janssen, SVB Leerink: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria, Research Funding. Shah: Bristol Myers Squibb: Research Funding; Janssen: Honoraria, Research Funding; Sanofi: Honoraria. Tan: Takeda: Research Funding; Sanofi: Honoraria; Janssen: Honoraria, Research Funding. Usmani: Genentech: Consultancy; Pfizer: Consultancy; Gracell: Consultancy; Sanofi: Consultancy, Research Funding; Abbvie: Consultancy, Research Funding; Bristol-Myers Squibb - Celgene: Consultancy, Research Funding; Gilead: Research Funding; EdoPharma: Consultancy; Bristol-Myers Squibb - Celgene:: Consultancy, Research Funding; Array Biopharma: Research Funding; Amgen: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; GSK: Consultancy, Research Funding; Merck: Research Funding; Pharmacyclics: Research Funding; Oncopeptides: Consultancy; Sanofi: Consultancy, Research Funding; SeaGen: Consultancy, Research Funding; SecuraBio: Consultancy; TeneoBio: Consultancy; SkylineDX: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Johnson & Johnson - Janssen: Consultancy, Research Funding.

*signifies non-member of ASH