-Author name in bold denotes the presenting author
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Clinically Relevant Abstract denotes an abstract that is clinically relevant.

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936 Comparative Safety and Efficacy of Ciltacabtagene Autoleucel and Idecabtagene Vicleucel CAR T-Cell Therapies in Relapsed or Refractory Multiple Myeloma

Program: Oral and Poster Abstracts
Type: Oral
Session: 907. Outcomes Research: Plasma Cell Disorders: Bispecific Antibodies and CAR-T Therapies in Myeloma-The Yin and Yang of Powerful Therapies
Hematology Disease Topics & Pathways:
Research, Clinical Research, Plasma Cell Disorders, Health outcomes research, Diseases, Therapy sequence, Real-world evidence, Treatment Considerations, Lymphoid Malignancies, Adverse Events
Monday, December 9, 2024: 4:00 PM

Doris K. Hansen, MD1, Lauren C. Peres, PhD, MPH2*, Danai Dima, MD3, Alicia Richards, PhD4*, Leyla O. Shune, MD5, Aimaz Afrough, MD6, Shonali Midha, MD7*, Binod Dhakal, MBBS8, Mehmet H. Kocoglu, MD9, Shebli Atrash, MD10, Chris Ferreri, MD10, Omar Castaneda, MD11, James A Davis, PharmD12*, Evguenia Ouchveridze, MD5, Joseph P. McGuirk, DO13, Charlotte B Wagner, PharmD14*, Radhika Bansal, MBBS15*, Patrick Costello, MS16*, Kinaya Smith, MD17*, Alex Lieberman-Cribbin18*, Gabriel De Avila19*, Sneha Purvey, MD20, Hitomi Hosoya, MD, PhD21, Lekha Mikkilineni, MD, MA22, Laura B. Oswald, PhD23*, Gurbakhash Kaur, MD, MA24, Oren Pasvolsky, MD25, Mahmoud R. Gaballa, MD26, Megan M Herr, PhD27, Peter A. Forsberg, MD28, Murali Janakiram, MBBS29, Myo Htut, MD29, Sireesha Asoori, MBBS, MPH30*, Nilesh Kalariya, PhD, RN25*, Hamza Sloan Hashmi, MD31*, Ran Reshef, MD, MSc32, Douglas W Sborov, MD33, Omar Nadeem, MD34, Faiz Anwer, MD35, Jack Khouri, MD36, Shahzad Raza, MD37, Djordje Atanackovic, MD38, Melissa Alsina, MD39,40*, Ciara Louise Freeman, PhD, MSc, FRCPC, MRCP11, Frederick L. Locke, MD41, Peter M. Voorhees, MD42, Larry D Anderson Jr., MD, PhD6, Shambavi Richard, MD18, Thomas Martin, MD30, Yi Lin, MD, PhD43, Krina K. Patel, MD, MSc44 and Surbhi Sidana, MD45

1H. Lee Moffitt Cancer Center & Research Institute, Tampa
2Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, FL
3Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH
4H. Lee Moffitt Cancer Center and Research Institute, Tampa
5University of Kansas Medical Center, Kansas City, KS
6Myeloma, Waldenstrom’s, and Amyloidosis Program, Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX
7Division of Hematologic Neoplasia, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA
8Division of Hematology and Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI
9University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, Baltimore, MD
10Levine Cancer Institute, Charlotte, NC
11Department of Blood and Marrow Transplantation and Cellular Immunotherapy, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL
12Division of Hematology-Oncology, Medical University of South Carolina, Charleston, SC
13Division of Hematologic Malignancies & Cellular Therapeutics, University of Kansas Medical Center, Kansas City, KS
14Division of Hematology and Hematologic Malignancies, Huntsman Cancer Institute at the University of Utah, Salt Lake City, UT
15Division of Hematology, Mayo Clinic, Bismarck, ND
16Dana-Farber Cancer Institute, Boston, MA
17Medical College of Wisconsin, Milwaukee, WI
18Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY
19H Lee Moffitt Cancer Center and Research Institute, Tampa, FL
20Virginia Commonwealth University, Richmond, VA
21Division of Bone Marrow Transplant & Cellular Therapy,, Stanford University, Palo Alto, CA
22Division of Blood and Marrow Transplant and Cellular Therapy, Stanford University, Palo Alto, CA
23Department of Health Outcomes and Behavior, Moffitt Cancer Center, Tampa, FL
24Division of Hematologic Malignancies and Cellular Therapy, Dept of Internal Medicine, Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX
25Department of Lymphoma & Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX
26The University of Texas MD Anderson Cancer Center, Houston, TX
27Roswell Park Comprehensive Cancer Center, Buffalo, NY
28University of Colorado, Aurora, CO
29Judy and Bernard Briskin Center for Multiple Myeloma Research, City of Hope, Duarte, CA
30UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA
31Myeloma Service, Division of Hematologic Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
32Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY
33Huntsman Cancer Institute, University of Utah, Salt Lake City, UT
34Center for Early Detection and Interception of Blood Cancers, Dana-Farber Cancer Institute, Boston, MA
35Cleveland Clinic Taussig Cancer Institute, Cleveland, OH
36Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH
37Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Overland Park, KS
38University of Maryland Greenebaum Comprehensive Cancer Center, Baltimore, MD
39Moffitt Cancer Center, Tampa, FL
40Department of Blood and Marrow Transplant and Cellular Immunotherapy, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL
41Department of Blood and Marrow Transplant and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, FL
42Plasma Cell Disorders Section, Department of Hematologic Oncology & Blood Disorders, Levine Cancer Center, Charlotte, NC
43Division of Hematology, Mayo Clinic, Rochester, MN
44M.D. Anderson Cancer Center, MD Anderson Cancer Center, Houston, TX
45Division of Blood and Marrow Transplantation and Cellular Therapy, Stanford University School of Medicine, Stanford, CA

Introduction. Ciltacabtagene autoleucel (cilta-cel) and idecabtagene vicleucel (ide-cel), two anti-B-cell maturation antigen (BCMA) CAR T therapies, have demonstrated remarkable responses and improved survival among patients with relapsed/refractory multiple myeloma (RRMM) in the clinical trials and standard of care (SOC) setting. Here, we compare safety, efficacy, and survival for patients treated with SOC ide-cel and cilta-cel.

Methods. Data were from a retrospective chart review of RRMM patients leukapheresed by 12/31/2022 with the intent to receive SOC ide- or cilta-cel at 19 institutions in the US Multiple Myeloma Immunotherapy Consortium. An inverse probability of treatment weighting (IPTW) approach was used to compare outcomes by therapy type (cilta- vs. ide-cel), balancing on age, sex, race and ethnicity, performance status, extramedullary disease, high-risk cytogenetics, prior BCMA therapy, bone marrow plasma cells, penta-refractory status, lymphodepleting chemotherapy, baseline ferritin, low cell dose, and bridging therapy response. Logistic regression and Cox proportional hazard models were used to examine the association of treatment type with safety, efficacy, and survival accordingly, while adjusting for IPTW weights. We employed propensity score matching utilizing the same covariates to identify the association of treatment type with progression-free survival (PFS) within relevant patient sub-groups.

Results. A total of 641 patients were leukapheresed by 12/31/2022 with ide-cel (n=386) and cilta-cel (n=255). 586 patients were infused (n=350 for ide-cel; n=236 for cilta-cel) with a median follow-up of 13.0 and 12.6 months, respectively. After IPTW, patient characteristics were well-balanced. Patients treated with cilta-cel were more likely to have grade ≥ 3 cytokine release syndrome (CRS) (OR=5.52, 95% CI=1.76-17.30, p=0.004), infections (OR=2.07, 95% CI=1.44-2.97, p<0.001), and delayed neurotoxicity (NT) (OR=20.97, 95% CI=4.75-92.42, p<0.001) compared to patients treated with ide-cel. In the cilta-cel cohort, 24 patients (10%) experienced delayed NT compared to 2 patients (1%) in the ide-cel cohort. Although not statistically significant, patients treated with cilta-cel were more likely to have any second primary malignancies (SPMs) (OR=1.87, 95% CI=0.94-3.71, p=0.08) and any SPMs excluding non-melanoma skin cancers (OR=1.78, 95% CI=0.78-4.10, p=0.2) but no association was observed for odds of hematologic SPMs (OR=0.98, 95% CI=0.26-3.61). No association was observed for therapy type with any or severe immune effector cell-associated neurotoxicity syndrome, any CRS, severe cytopenias, and non-relapse mortality.

Compared to ide-cel, cilta-cel was associated with better treatment responses of ≥ complete response (OR=2.38, 95% CI=1.61-3.51, p<0.001) and ≥ partial response (OR=1.74, 95% CI=0.99-3.05, p=0.06). Patients treated with cilta-cel had a longer PFS and overall survival (OS) than ide-cel (HR=0.47, 95% CI=0.35-0.62, p<0.001 and HR=0.63, 95% CI=0.42-0.93, p=0.02, respectively), and these findings were similar in the intention to treat cohort (PFS: HR=0.44, 95% CI=0.34-0.55, p<0.001; OS: HR=0.55, 95% CI=0.41-0.73, p<0.001, respectively). We observed consistent findings when repeating the analyses restricting the ide-cel cohort to patients infused during the same time-period as FDA approval for cilta-cel (≥ March 2022), restricting to patients with data on all covariates, and restricting to sites that contributed data for both products. In a propensity matched population, (n=380; n=190 for cilta-cel and n=190 for ide-cel), patients treated with cilta-cel had superior PFS compared to those treated with ide-cel in most subgroups with respect to age and disease characteristics including extramedullary disease, high-risk cytogenetics, and elevated baseline ferritin (p<0.05).

Conclusion. Our results suggest superior efficacy of cilta-cel with a higher incidence of certain toxicities compared to ide-cel in the SOC setting. This study provides valuable information for patient counseling and guiding the selection of CAR T-cell therapy for specific patient populations. Further validation through similar large-scale real-world experiences or prospective studies is needed to confirm our results and enhance applicability in the clinical setting.

*DH, LP, & DD are co-first authors

* YL, KP, & SS are co-last authors

Disclosures: Hansen: Pfizer: Consultancy; Karyopharm: Consultancy, Research Funding; Janssen: Consultancy; BMS: Consultancy, Research Funding. Peres: Karyopharm Therapeutics: Research Funding; Bristol Myers Squibb: Research Funding. Shune: BMS: Membership on an entity's Board of Directors or advisory committees; Norvatis: Membership on an entity's Board of Directors or advisory committees; Johnson and Johnson: Membership on an entity's Board of Directors or advisory committees. Afrough: K36 Therapeutics: Research Funding; Bristol-Myers Squibb: Honoraria, Other; Sanofi: Honoraria, Other; Karyopharm Therapeutics: Honoraria, Other; Adaptive Biotech: Research Funding; Abbvie: Research Funding. Midha: Janssen: Consultancy; Pfizer: Consultancy. Dhakal: Bristol Myers Squibb: Honoraria, Research Funding; Acrellx: Research Funding; Carsgen: Research Funding; Medical College of Wisconsin: Current Employment; Genentech: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria, Speakers Bureau; Karyopharm: Honoraria, Speakers Bureau; Sanofi: Research Funding; C4 therapeutics: Research Funding; Janssen: Honoraria, Research Funding, Speakers Bureau. Atrash: Janssen: Honoraria; Karyopharm: Research Funding; Amgen: Research Funding; GSK: Research Funding. Ferreri: Affimed Therapeutics.: Current equity holder in private company; Janssen: Consultancy; Sanofi: Consultancy. Castaneda: Janssen: Consultancy; Legend Biotech: Consultancy; BMS: Consultancy. Davis: Janssen Biotech: Speakers Bureau. McGuirk: Sana technologies: Consultancy; Legend biotech: Consultancy; NEKTAR therapeutics: Consultancy; Envision: Consultancy; Caribou bio: Consultancy; CRISPR therapeutics: Consultancy; Autolus: Consultancy; Allo Vir: Consultancy; Novartis: Consultancy; Kite: Consultancy; BMS: Consultancy. Wagner: Jazz: Research Funding; Pfizer: Consultancy. Bansal: Kite Pharma: Other: Travel Support. Mikkilineni: Legend Biotech: Consultancy, Other: advisory board at ASH December 2023; BiolineRx: Consultancy, Other: advisory board at ASH December 2023. Kaur: Kite, a Gilead Company: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Honoraria; Kedrion: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Arcellx: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Cellectar Biosciences: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Research Funding. Gaballa: GLG: Consultancy; Guidepoint: Consultancy; Boxer Capital, LLC: Consultancy; Bristol Myers Squibb: Consultancy. Forsberg: Karyopharm: Research Funding; Johnson and Johnson, BMS: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; University of Colorado: Ended employment in the past 24 months; Colorado Blood Cancer Institute: Current Employment. Janakiram: JANNSEN: Honoraria, Research Funding; BMS: Honoraria, Research Funding; LEGEND: Honoraria, Research Funding; FATE THERAPEUTICS: Research Funding. Hashmi: Karyopharm: Consultancy; Amgen: Consultancy; Janssen: Consultancy. Reshef: Synthekine: Research Funding; Sanofi: Research Funding; CareDx: Research Funding; Precision Biosciences: Research Funding; Bayer: Consultancy; Orca Bio: Consultancy; Incyte: Consultancy, Research Funding; TScan: Consultancy, Research Funding; Autolus: Consultancy; Quell Biotherapeutics: Consultancy; Sana Biotechnology: Consultancy; J&J: Research Funding; Genentech: Research Funding; Cabaletta: Research Funding; BMS: Research Funding; Gilead Sciences: Consultancy, Research Funding; TCR2: Research Funding; Atara Biotherapeutics: Research Funding; Immatics: Research Funding; Abbvie: Research Funding; Takeda: Research Funding; Allogene: Consultancy. Sborov: University of Utah, Huntsman Cancer Institute: Current Employment; Genentech, Inc.: Consultancy; Binaytara Foundation: Honoraria; Sanofi: Consultancy; Bristol Myers Squibb: Consultancy; GlaxoSmithKline: Consultancy; Abbvie: Consultancy; Parexel, Keosys: Other: IRC; Society of Utah Medical Oncology: Membership on an entity's Board of Directors or advisory committees; Arcellx: Consultancy; AstraZeneca: Consultancy; Bioline: Consultancy; Pfizer: Consultancy, Research Funding; Janssen: Consultancy; Legend Biotech: Consultancy. Nadeem: Sanofi: Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria; GPCR Therapeutics: 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; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; JNJ: Research Funding. Anwer: BMS: Consultancy. Khouri: GPCR Therapeutics: Honoraria; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy; Legend Biotech: Honoraria. Raza: Kite Pharma: Consultancy; Pfizer: Consultancy; Prothena Biosciences: Consultancy. Alsina: Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees. Freeman: Seattle Genetics: Consultancy; Abbvie: Consultancy; Celgene: Consultancy; BMS: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy; Incyte: Consultancy; Amgen: Consultancy; Roche/Genentech: Research Funding; Janssen: Consultancy, Research Funding; ONK therapeutics: Consultancy. Locke: ecoR1: Consultancy; GammaDelta Therapeutics: Consultancy; BioPharma: Honoraria; Aptitude Health: Honoraria; Legend Biotech: Consultancy; Gilead Company: Consultancy; BMS: Consultancy, Research Funding; Emerging Therapy Solutions Gerson Lehman Group: Consultancy; ASH: Honoraria, Other: Travel support; Celgene: Consultancy; Cowen: Consultancy; Amgen: Consultancy; Pfizer: Consultancy; Communications CARE Education: Honoraria; iMedX: Honoraria; Society for Immunotherapy of Cancer: Honoraria; A2: Consultancy; Leukemia and Lymphoma Society Scholar in Clinical Research: Research Funding; National Cancer Institute: Research Funding; Wugen: Consultancy; Clinical Care Options Oncology: Honoraria; Novartis: Consultancy, Research Funding; Moffit Cancer Center: Patents & Royalties: cellular immunotherapy; Bluebird Bio: Consultancy, Research Funding; Umoja: Consultancy; Gerson Lehrman Group (GLG): Consultancy; Sana: Consultancy; 2SeventyBio: Research Funding; Caribou: Consultancy; CERo Therapeutics: Research Funding; Cellular Biomedicine Group: Consultancy; Iovance: Consultancy; Janssen: Consultancy; Kite, a Gilead Company: Consultancy, Other: Travel support, Research Funding; Allogene: Consultancy, Research Funding; Calibr: Consultancy; Aptitude Health: Honoraria. Voorhees: Lava Therapeutics: Consultancy; Regeneron: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Consultancy; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Research Funding; GSK: Consultancy, Research Funding; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Anderson: Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Cellectar Biosciences: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Prothena: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: DSMB; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Beigene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Honoraria, Other: Travel Expenses, Research Funding. Richard: Heidelberg Pharma: Research Funding; C4 Therapeutics: Research Funding; Gracell Therapeutics: Other: Steering Committee, Research Funding; Genentech: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Steering Committee, Research Funding. Martin: Roche: Honoraria; Sanofi: Research Funding; Janssen: Research Funding; Pfizer: Honoraria; BMS: Research Funding; GSK: Honoraria; AMGEN: Research Funding. Lin: NexImmune: Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; Regeneron: Consultancy; Caribou: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Genentech: Consultancy; Janssen: Consultancy, Research Funding; Legend: Consultancy; Celgene: Consultancy, Research Funding. Patel: BMS: Consultancy, Other: chair of scientific advisory board ; Sanofi: Consultancy; Takeda: Consultancy; Poseida: Consultancy; Caribou Sciences: Consultancy; Johnson & Johnson (Janssen): Consultancy; AstraZeneca: Consultancy; Kite, A Gilead company: Consultancy, Other: scientific advisory board; Pfizer: Consultancy; Abbvie: Consultancy; Merck: Consultancy; Genentech: Consultancy; Oricel: Consultancy, Other: Chair of scientific board. Sidana: Takeda: Consultancy; Janssen: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Regeneron: Consultancy; Legend: Consultancy; BiolineRx: Consultancy; Sanofi: Consultancy; Pfizer: Consultancy; Abbvie: Consultancy; Oncopeptides: Consultancy; Novartis: Research Funding; Kite, A Gilead company: Consultancy.

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*signifies non-member of ASH