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4659 Idecabtagene Vicleucel Chimeric Antigen Receptor T-Cell Therapy for Relapsed/Refractory Multiple Myeloma with Renal Insufficiency: 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, epidemiology, Clinical Research, Plasma Cell Disorders, Chimeric Antigen Receptor (CAR)-T Cell Therapies, Diseases, Therapies, registries, Lymphoid Malignancies
Monday, December 12, 2022, 6:00 PM-8:00 PM

Surbhi Sidana, MD1, Lauren C. Peres, PhD, MPH2*, Hamza Hashmi, MD3, Hitomi Hosoya, MD, PhD4, Christopher J. Ferreri, MD5, Shebli Atrash, MD6, Jack Khouri, MD7, Peter M. Voorhees, MD6, Danai Dima, MD8, Gary Simmons, DO9, Nilesh Kalariya5*, Vanna Hovanky10*, Sushma Bharadwaj, MD, MS11*, Sally Arai, MD12, David B. Miklos, MD, PhD11, Charlotte B Wagner, PharmD13*, James Davis, PharmD3*, Douglas W. Sborov, MD14, Taiga Nishihori, MD15, Melissa Alsina, MD**16, Frederick L. Locke, MD17, Rebecca Gonzalez, PharmD, BCOP17*, M. Hakan Kocoglu, MD18, Aishwarya Sannareddy, MBBS19*, Aimaz Afrough, MD20, Joseph P. McGuirk, DO21, Leyla O. Shune, MD21, Krina Patel, MD, MSc22 and Doris K. Hansen, MD15

1Division of Blood and Marrow Transplantation and Cellular Therapy, Department of Medicine, Stanford University School of Medicine, Stanford, CA
2H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL
3Department of Hematology/Medical Oncology, Medical University of South Carolina, Charleston, SC
4Divisions of Oncology and Hematology, Department of Medicine, Stanford University School of Medicine, Stanford, CA
5The University of Texas MD Anderson Cancer Center, Houston, TX
6Levine Cancer Institute, Charlotte, NC
7Department of Hematology and Medical Oncology, Cleveland Clinic, Taussig Cancer Institute, Cleveland, OH
8Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH
9Virginia Commonwealth University Massey Cancer Center, Richmond, VA
10Department of Medicine, Division of Blood and Marrow Transplantation and Cellular Therapy, Stanford University, Stanford, CA
11Division of BMT and Cellular Therapy, Stanford University, Stanford, CA
12Division of BMT and Cellular Therapy, Stanford University School of Medicine, Stanford, CA
13University of Utah Huntsman Cancer Institute, Salt Lake City, UT
14Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT
15Department of Blood and Marrow Transplant and Cellular Immunotherapy, H. Lee Moffitt Cancer Center, Tampa, FL
16Moffitt Cancer Center, Tampa, FL
17Department of Blood and Marrow Transplant and Cellular Immunotherapy, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL
18University of Maryland Greenebaum Comprehensive Cancer Center, Baltimore, MD
19Division of Hematologic Malignancies, UT Southwestern Harold C. Simmons Comprehensive Cancer Center, Dallas, TX
20Division of Hematologic Malignancies and Cellular Therapy, Dept of Internal Medicine, Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX
21The University of Kansas Medical Center, Kansas City, KS
22Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX

Introduction: Idecabtagene vicleucel (ide-cel) is an autologous BCMA directed chimeric antigen receptor therapy T (CAR-T) cell therapy approved for relapsed/refractory multiple myeloma (RRMM). However, patients with renal insufficiency (RI) were excluded from the registrational KarMMa clinical trial. RI impacts a significant proportion of patients with multiple myeloma and the safety and efficacy profile of CAR-T remains unknown in this patient population. We evaluated the real-world outcomes of patients with RI treated with standard of care ide-cel.

Methods: RI was defined as creatinine clearance (CrCl) < 50 ml/min at the time of CAR-T therapy. CrCl of < 30 ml/min or being on dialysis was defined as severe RI. Dosing of lymphodepletion chemotherapy and grading/management of toxicities was per institutional guidelines, while responses were graded based on the IMWG response criteria.

Results: The study cohort includes 211 patients receiving ide-cel from 11 medical centers, of which 28 (13%) patients had RI at the time of CAR-T therapy with CrCl < 50 ml/min. Among these, 11 (39%) patients had severe RI including one patient on dialysis. Table 1 describes baseline and treatment characteristics of patients with and without RI. Patients with RI were older (69 vs 63 years, p=0.003) and more likely to be female (68% vs 35%, p=0.001). They had lower albumin, higher beta-2-microglobulin (B2M) and higher likelihood of having revised ISS stage 3 disease, driven primarily by high B2M levels. Median prior lines of therapy in patients with and without RI was 8 vs 6, respectively. Fludarabine was dose reduced in 82% patients with RI and amongst this group 61% of patients had > 20% dose reduction. There was no difference in CAR-T cell dose infused (median: 416 vs 408 million cells).

Cytokine release syndrome (CRS) was seen in 89% vs 84%, p=0.7 of patients with and without RI, including grade ≥ 2 CRS in 14% vs 20%, p=0.6 of patients, respectively. Neurotoxicity was observed in 21% vs 19%, p=0.7 of patients, respectively. Patients with RI had a longer hospital stay (median 13 vs 9 days, p=0.05), although ICU admission rates were similar (14% vs 7%, p=0.3). Infections were seen in 43% vs 32%, p=0.2 of patients, respectively. At one month, any ≥ grade 3 cytopenia was more common in patients with RI (86% vs 55%, p=0.001), including grade ≥ 3 neutropenia (54% vs 33%, p=0.04) and grade ≥ 3 thrombocytopenia (75% vs 41%, p<0.001). By 90 days post CAR-T, there was no difference in > grade 3 cytopenias amongst the 2 groups. Renal function did not significantly change after CAR-T in most patients. Amongst patients with paired baseline and day 30 data, no patient with CrCl 30-49 ml/min experienced worsening of CrCl to < 30 ml/min at day 30. Amongst 10 patients with CrCl < 30 ml/min, 3 patients experienced improvement in CrCl to 30-49 ml/min, while 7 patients had similar CrCl at day 30. New need for dialysis post CAR-T was observed in two patients, both with baseline CrCl > 50 ml/min; in one patient at 1 week post CAR-T in the setting of critical illness/severe CRS and in another patient 8 months post CAR-T in the setting of salvage therapy for relapse and critical illness. 34 patients have died by last follow-up, of which 8 were due to CAR-T related toxicities including infections (1 patient with RI, 7 without RI, p=0.9).

189 patients were evaluable for response. Patients with RI had an overall response rate of 96% comparted to 83% in patients without RI, p=0.045. Complete response (58% vs 65%, p=0.1) and very good partial response rates (77% vs 65%, p=0.2) were similar. At a median follow-up of 6 months, the median progression-free survival (PFS) in the two groups was 6.5 vs 8.1 months, p=0.6 (Fig 1). On multivariable analysis incorporating RI, age, cytogenetics and prior BCMA-directed therapy, RI was not an independent predictor for PFS (HR 1.4, 95% CI: 0.7-2.7, p=0.4), while high-risk disease, prior BCMA therapy, and age < 65 years were independent adverse prognostic factors.

Conclusions: This multicenter retrospective study supports the feasibility of ide-cel CAR-T cell therapy in RRMM patients with RI. CRS, neurotoxicity and non-relapse mortality were comparable in patients with or without RI, although patients with RI had a longer hospital stay and were more likely to experience short-term high-grade cytopenias. Importantly, patients with RI experienced similar benefit in terms of response rates and PFS.

S.S & L.P: co-first authors. L.S, K.K.P & D.K.H: joint senior authors

Disclosures: Sidana: Oncopeptides: Consultancy; Bristol Myers Squibb: Consultancy, Research Funding; Allogene: Research Funding; Janssen: Consultancy, Research Funding; Sanofi: Consultancy; Prothena: Honoraria; Magenta Therapeutics: Consultancy, Research Funding. Hashmi: Sanofi: Consultancy, Speakers Bureau; GSK: Speakers Bureau; BMS: Consultancy; KARYOPHARM: Speakers Bureau; JANSSEN: Consultancy. Ferreri: Sanofi: Membership on an entity's Board of Directors or advisory committees; Affimed: Current equity holder in publicly-traded company. Atrash: GSK: Honoraria, Research Funding; Celgene: Honoraria, Speakers Bureau; Takeda: Honoraria; Sanofi: Honoraria, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Amgen: Research Funding. Simmons: Kite/Gilead: Speakers Bureau. Arai: Kadmon: Membership on an entity's Board of Directors or advisory committees. Miklos: Bristol Meyers Squibb: Consultancy; Allogene: Research Funding; Fosun Kite: Consultancy, Honoraria; Pharmacyclics: Patents & Royalties: cGVHD Ibrutinib patent ; Novartis: Consultancy; Kite, a Gilead Company: Research Funding; Adaptive Biotech: Consultancy; Janssen: Consultancy, Honoraria. Wagner: Abbvie Inc.: Other: Partner is currently employed as a Medical Science Liaison . Sborov: GSK: Consultancy, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy; Pfizer: Consultancy; Amgen: Consultancy; Bioline: Consultancy; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy; Sanofi: Consultancy. Alsina: BMS: Research Funding; BMS, Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Locke: Daiichi Sankyo: Consultancy; Takeda: Consultancy; Sana: Consultancy; CERo Therapeutics: Research Funding; ), National Cancer Institute: Research Funding; Leukemia and Lymphoma Society: Research Funding; Aptitude Health: Other: Education or editorial activity; ASH: Other: Education or editorial activity; BioPharm Communications: Other: Education or editorial activity; CAREducation: 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; 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. McGuirk: In8bio, Inc.: Other: IIT Clinical Trial; Sana: Honoraria; Juno Therapeutics: Consultancy, Honoraria, Research Funding; CRISPR Therapeutics: Consultancy; Orca Bio: Research Funding; Kite, a Gilead Company: Consultancy, Honoraria, Research Funding, Speakers Bureau; Allovir: Consultancy, Honoraria, Research Funding, Speakers Bureau; BMS: Consultancy, Honoraria, Speakers Bureau; Magenta Therapeutics: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria; Nextar: Consultancy, Honoraria. Patel: Legend, Pfizer, Celgene, Merck, Poseida, PrecisionBi Arcellx, Caribou, Nektar, oncopeptides: Consultancy. 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.

*signifies non-member of ASH