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4677 Absolute Lymphocyte Count and Outcomes of Multiple Myeloma Patients Treated with Idecabtagene Vicleucel: The U.S. Myeloma CAR T Consortium Real World Experience

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, Clinical Research, Plasma Cell Disorders, Chimeric Antigen Receptor (CAR)-T Cell Therapies, Diseases, real-world evidence, Therapies, Immunotherapy, Lymphoid Malignancies, Study Population, Human
Monday, December 12, 2022, 6:00 PM-8:00 PM

Jack Khouri, MD1, Hong Li, MS2*, Doris K. Hansen, MD3, Surbhi Sidana, MD4, Leyla O. Shune, MD5, Shaun DeJarnette6*, Faiz Anwer, MD1*, Douglas W Sborov7*, Charlotte B Wagner, PharmD7*, M. Hakan Kocoglu, MD8, Shebli Atrash, MD9, Peter M. Voorhees, MD10, Jason Valent, MD1, Lauren C. Peres, PhD, MPH11*, Vanna Hovanky12*, Gary Simmons, DO13, Danai Dima, MD1, Nilesh Kalariya14*, Aimaz Afrough, MD15, Gurbakhash Kaur, MD16*, Aishwarya Sannareddy, MBBS17*, Christopher J. Ferreri, MD14, James Davis, PharmD18*, Joseph P. McGuirk, DO19, Frederick L. Locke, MD20, Rachid C. Baz, MD21, Betty K. Hamilton, MD22, Melissa Alsina, MD**23, Craig S. Sauter, MD24*, Hamza Hashmi, MD18 and Krina Patel, MD, MSc25

1Department of Hematology and Medical Oncology, Cleveland Clinic, Taussig Cancer Institute, Cleveland, OH
2Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH
3Department of Blood and Marrow Transplant and Cellular Immunotherapy, H. Lee Moffitt Cancer Center, Tampa, FL
4Stanford University School of Medicine, Stanford, CA
5Division of Hematologic Malignancies and Cellular Therapeutics (HMCT), University of Kansas Medical Center, Kansas City, KS
6Kansas University Medical Centre, Kansas City
7University of Utah Huntsman Cancer Institute, Salt Lake City, UT
8University of Maryland Greenebaum Comprehensive Cancer Center, Baltimore, MD
9Levine Cancer Institute, Charlotte, NC
10Plasma Cell Disorders Section, Department of Hematologic Oncology & Blood Disorders, Levine Cancer Center, Charlotte, NC
11H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL
12Department of Medicine, Division of Blood and Marrow Transplantation and Cellular Therapy, Stanford University, Stanford, CA
13Virginia Commonwealth University Massey Cancer Center, Richmond, VA
14The University of Texas MD Anderson Cancer Center, Houston, TX
15Division of Hematologic Malignancies and Cellular Therapy, Dept of Internal Medicine, Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX
16Division of Hematology/Oncology, Department of Internal Medicine, University of Texas Southwestern, Dallas, TX
17Division of Hematology and Oncology, UT Southwestern Medical Center, Dallas, TX
18Department of Hematology/Medical Oncology, Medical University of South Carolina, Charleston, SC
19Division of Hematologic Malignancies & Cellular Therapeutics, University of Kansas Medical Center, Kansas City, KS
20Department of Blood and Marrow Transplant and Cellular Immunotherapy, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL
21Department of Malignant Hematology, Moffitt cancer center and research institute, tampa, FL
22Blood and Marrow Transplant Program, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH
23Moffitt Cancer Center, Tampa, FL
24Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic Foundation, Cleveland Clinic, Cleveland, OH
25Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX

Introduction: Chimeric Antigen Cell (CAR) T-cell therapy with idecabtagene vicleucel (ide-cel) is FDA approved for relapsed refractory multiple myeloma (MM). Investigating factors that may predict response, toxicity and survival is important to guide therapy and inform prognosis. Low pre-lymphodepletion (LD) absolute lymphocyte count (ALC) was found to be associated with worse outcomes in a small cohort of patients (pts) treated with ide-cel (Liu et al. Transplant Cell Ther 2022). We evaluated the impact of pre-apheresis (pre-A) and pre-LD peripheral blood ALC on post-ide-cel outcomes in a large patient cohort.

Methods: A total of 215 myeloma pts were treated with ide-cel at 11 U.S. academic medical centers. We studied the effect of ALC including pre-A, pre-LD, absolute and percent reduction in ALC between apheresis and LD on progression free survival (PFS), overall survival (OS), overall hematologic response rate (ORR which included VGPR, CR and sCR) and cytokine release syndrome (CRS) incidence. Associations of ALC parameters with PFS and OS were evaluated using Kaplan-Meier (KM) method and Cox proportional hazard model. Patient demographics and clinical characteristics between ALC groups were compared using Chi square test and Wilcoxon rank test.

Results: The median patient age was 64 years (range, 36-83) and 60 % were male. The median prior lines of therapy was 6 (IQR, 5-9), 84.2% had a prior autologous hematopoietic cell transplant (AHCT), 44.7% had extramedullary disease, and 77.1% received bridging therapy (BT). CRS was seen in 81.1% of the pts, mostly grade 1. The median pre-A and pre-LD ALC’s were 0.65 x109/L (range, 0.06-5.3) and 0.55 (range, 0-5.0), respectively. The pre-A ALC was significantly higher than pre-LD ALC (mean difference and 95% CI: 0.10 (0.04, 0.40), p=0.002). The median follow-up time after CAR-T infusion was 5.4 (IQR, 2.1-8.3) months. Pre-A and pre-LD ALC’s were not significantly associated with PFS or OS, while pts with a high absolute reduction in ALC between apheresis and LD (≥0.27 or top quartile) had a significantly worse six-month PFS (48.4 vs 63.5%, p= 0.04) and OS (76.0 vs 87.7%, p= 0.03). Similarly, patients with a high percent reduction between pre-A and pre-LD ALC (≥37.5% or top quartile) had a worse six-month PFS (41.9 vs 65%, p <0.001) and OS (70.5 vs 89%, P=0.001). PFS and OS differences remained statistically significant after adjusting for age, race, CRS grade, ECOG-PS, extramedullary disease and prior AHCT. Kaplan-Meier estimated PFS and OS curves for absolute ALC reduction groups and percent ALC reduction groups are displayed in Figure 1. The one-month and three-month ORR, and CRS grade were not significantly different between pre-A (≥1 or <1), pre-LD (≥1 or <1), absolute reduction and percent reduction ALC groups. ECOG-PS ≥2 (p= 0.004), ISS III (p= 0.015), and implementation of BT (p <0.01) were found to be associated with high ALC reduction or percent reduction. There was no difference in ALC between pts who received BT vs not. However, more patients in the high ALC reduction (>=0.27: 90.4% vs 72.6%, p=0.008) and high ALC percent reduction (>=37.5: 96.2% vs 70.5%) groups received BT. Moreover, pts who received BT had a worse PFS (six-month PFS: 53.2% vs 85.3%, p <0.001) and OS (six-month OS: 81.9% vs 95.8%, p= 0.02) likely indicating aggressive disease biology. The specific types of BT were not available in our dataset.

Conclusion: Pre-apheresis ALC did not impact survival in this large cohort of myeloma patients treated with ide-cel. Reduction in ALC between apheresis and lymphodepletion is a potentially predictive tool of survival outcomes and may be associated with more aggressive disease biology and the need for more aggressive bridging therapy. Investigating the association between specific types of bridging therapy, ALC reduction and outcomes may guide clinical decision making in this heavily pretreated myeloma patient population.

Disclosures: Hansen: BMS IMW Ide-Cel Academic Advisory Board: Membership on an entity's Board of Directors or advisory committees, Research Funding; Survivorship: Honoraria; OncLive: Honoraria. Sidana: Bristol Myers Squibb: Consultancy, Research Funding; Allogene: Research Funding; Janssen: Consultancy, Research Funding; Sanofi: Consultancy; Oncopeptides: Consultancy; Magenta Therapeutics: Consultancy, Research Funding; Prothena: Honoraria. Sborov: Skyline Dx, Janssen, AbbVie, Sanofi: Consultancy; GlaxoSmithKline, Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy. Wagner: Abbvie Inc.: Other: Partner is currently employed as a Medical Science Liaison . Atrash: Takeda: Honoraria; Sanofi: Honoraria, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; GSK: Honoraria, Research Funding; Celgene: Honoraria, Speakers Bureau; Amgen: Research Funding. Valent: Alexion, AstraZeneca Rare Disease: Research Funding. Simmons: Kite/Gilead: Speakers Bureau. Ferreri: Sanofi: Membership on an entity's Board of Directors or advisory committees; Affimed: Current equity holder in publicly-traded company. McGuirk: BMS: Consultancy, Honoraria, Speakers Bureau; Nextar: Consultancy, Honoraria; Orca Bio: Research Funding; Novartis: Consultancy, Honoraria; Magenta Therapeutics: Consultancy, Honoraria, Research Funding; Kite, a Gilead Company: Consultancy, Honoraria, Research Funding, Speakers Bureau; Allovir: Consultancy, Honoraria, Research Funding, Speakers Bureau; Juno Therapeutics: Consultancy, Honoraria, Research Funding; Sana: Honoraria; CRISPR Therapeutics: Consultancy; In8bio, Inc.: Other: IIT Clinical Trial. Locke: CERo Therapeutics: Research Funding; Takeda: Consultancy; Sana: Consultancy; Daiichi Sankyo: Consultancy; Aptitude Health: Other: Education or editorial activity; Clinical Care Options Oncology: Other: Education or editorial activity; Imedex: Other: Education or editorial activity; Society for Immunotherapy of Cancer: Other: Education or editorial activity; ), National Cancer Institute: Research Funding; Leukemia and Lymphoma Society: Research Funding; CAREducation: Other: Education or editorial activity; BioPharm Communications: Other: Education or editorial activity; ASH: Other: Education or editorial activity; BMS: Research Funding; A2: Consultancy; Celgene: Consultancy; Other: Patents & Royalties: patents, royalties, other intellectual property from several patents held by the institution in my name (unlicensed) in the field of cellular immunotherapy.; Wugen: Consultancy; Umoja: Consultancy; Novartis: Consultancy, Research Funding; Legend Biotech: Consultancy; Kite, a Gilead Company: Consultancy, Research Funding; Janssen: Consultancy; Iovance: Consultancy; GammaDelta Therapeutics: Consultancy; Emerging Therapy Solutions Gerson Lehrman Group: Consultancy; EcoR1: Consultancy; Cowen: Consultancy; Calibr: Consultancy; Cellular Biomedicine Group: Consultancy; Bristol Myers Squibb/Celgene: Consultancy; Bluebird Bio: Consultancy, Research Funding; Allogene: Consultancy, Research Funding; Amgen: Consultancy. Baz: Pfizer: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Shattuck labs: Membership on an entity's Board of Directors or advisory committees; genentech: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees, Research Funding; karyopharm: Research Funding; celgene: Consultancy, Honoraria; GSK: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy, Honoraria; Merck: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding. Hamilton: Syndax: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees; Kadmon: Membership on an entity's Board of Directors or advisory committees; Nkarta: Membership on an entity's Board of Directors or advisory committees; Equilium: Membership on an entity's Board of Directors or advisory committees; Mallinkrodt: Speakers Bureau. Alsina: BMS: Research Funding; BMS, Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Sauter: Genzyme/Sanofi: Other: PI; Precision Biosciences: Other: PI; BMS: Other: PI; Gamida Cell: Consultancy; CSL Behring: Consultancy; Ono Pharmaceuticals: Consultancy; Kite Pharma Inc.: Consultancy; Karyopharm Therapeutics Inc.: Consultancy. Hashmi: JANSSEN: Consultancy; KARYOPHARM: Speakers Bureau; GSK: Speakers Bureau; Sanofi: Consultancy, Speakers Bureau; BMS: Consultancy. Patel: Legend, Pfizer, Celgene, Merck, Poseida, PrecisionBi Arcellx, Caribou, Nektar, oncopeptides: Consultancy.

*signifies non-member of ASH