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
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.
See more of: Oral and Poster Abstracts