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766 Idecabtagene Vicleucel (Ide-cel) Chimeric Antigen Receptor (CAR) T-Cell Therapy in Patients with Relapsed/Refractory Multiple Myeloma (RRMM) Who Have Received a Prior BCMA-Targeted Therapy: Real World, Multi-Institutional Experience

Program: Oral and Poster Abstracts
Type: Oral
Session: 705. Cellular Immunotherapies: Real World Outcomes and Special Populations Treated with Cellular Therapy
Hematology Disease Topics & Pathways:
Research, Biological therapies, Clinical Research, Plasma Cell Disorders, Chimeric Antigen Receptor (CAR)-T Cell Therapies, Diseases, real-world evidence, Therapies, therapy sequence, Lymphoid Malignancies
Monday, December 12, 2022: 11:15 AM

Christopher J. Ferreri, MD1, Michelle A.T. Hildebrandt, PhD1, Hamza Hashmi, MD2, Leyla O. Shune, MD3, Joseph P. McGuirk, DO4, Douglas W. Sborov, MD5, Charlotte B Wagner, PharmD6*, M. Hakan Kocoglu, MD7, Shebli Atrash, MD8, Peter M. Voorhees, MD9, Jack Khouri, MD10, Danai Dima, MD10, Aimaz Afrough, MD11, Aishwarya Sannareddy, MBBS12*, Gary Simmons, DO13, James Davis, PharmD2*, Nilesh Kalariya1*, Lauren C. Peres, PhD, MPH14*, Melissa Alsina, MD**15, Frederick L. Locke, MD16, Surbhi Sidana, MD17, Doris K. Hansen, MD18, Krina Patel, MD, MSc19 and Omar Alexis Castaneda Puglianini, MD20

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

Background: Ide-cel received regulatory approval for the treatment of patients with RRMM after ≥4 prior lines of therapy based on the results of the pivotal KarMMa trial in which patients achieved an overall response rate (ORR) of 73%, ≥ complete response (CR) in 33%, and median progression free survival (PFS) of 8.8 months (Munshi et al. N Engl J Med 2021). Patients who had previously received a BCMA-targeted therapy (BCMA-TT) were excluded from the KarMMa trial. We evaluated the real-world outcomes for patients treated with standard of care ide-cel after having previously received a BCMA-TT.

Methods: Eleven US academic centers contributed data to this effort which included patients who had undergone apheresis up until 5/1/2022, and who were infused with ide-cel with sufficient follow-up duration for at least a day 30 response assessment. Patients who died from an infection or ide-cel related toxicity prior to response assessment were included in the safety and survival analyses, but were not considered evaluable for response.

Results: A total of 50 patients who had received a prior BCMA-TT and were later infused with ide-cel were evaluable for safety and survival analyses, of which 49 were evaluable for response. The specific type of prior BCMA-TT with respective ORR to the prior BCMA-TT were antibody-drug conjugates (n=38, ORR 17%), bispecifics (n=7, ORR 0%), and CAR T (n=5, ORR 80%). This cohort consisted of 56% patients aged ≥ 65 years, 66% male, and 19% with ECOG performance status ≥ 2. Disease characteristics were notable for 36% with high-risk FISH findings as defined by del(17p), t(4;14), and t(14;16), 50% extramedullary disease, 27% R-ISS stage III disease, and 30% with high bone marrow plasma cell burden (≥50%) prior to ide-cel infusion. Patients were heavily pre-treated with a median of 9 prior lines of therapy, 88% received prior autologous stem cell transplant, 62% were penta-refractory, and 86% required bridging therapy (68% with ≥SD on bridging therapy). Compared to the cohort of patients who had not received a prior BCMA-TT (n=153), patients who received prior BCMA-TT were more likely to have t(4;14) as a high-risk feature (23% v 8%; p=0.005), had a higher median number of prior lines of therapy (9 v 6; p<0.0001), and were more likely to have penta-refractory disease (62% v 37%; p=0.002).

Response outcomes stratified by the specific type of prior BCMA-TT and by timing of prior BCMA-TT are summarized in Table 1. Patients receiving prior BCMA-TT had a lower ORR (74% v 88%; p=0.021) and lower best response of ≥ CR (29% v 48%; p=0.018) compared to those without prior BCMA-TT. Compared to patients who were treated with a BCMA-TT > 6 months prior to ide-cel, those with treatment < 6 months prior to ide-cel had lower rates of overall response (60% v 83%; p=0.076), CR (20% v 34.5%; p=0.22), and median PFS (3.0 v 5.3 months; p=0.39), though these differences did not reach statistical significance. Treatment with a prior BCMA-TT was associated with an inferior median PFS compared to those without prior BCMA-TT (3.2 v 9.0 months; log-rank p=0.0002). The 3-month PFS rates amongst those with prior ADC, prior bispecific, prior CAR T, and without prior BCMA-TT were 57.2%, 41.5%, 77.8%, and 85% respectively. On univariate analysis amongst patients treated with a prior BCMA-TT, having penta-refractory disease reached borderline significance for association with response of < PR (p=0.053), and treatment with a prior ADC trended for association with a response of < CR compared to other modalities of BCMA-TT (p=0.076).

The toxicity profile for patients receiving a prior BCMA-TT was similar to those in our cohort who had not received a prior BCMA-TT and to that described in KarMMa. Grade ≥ 3 CRS and ICANS were 2.0% and 8.5% respectively. Patients in the prior BCMA-TT cohort were more likely to have grade 4 thrombocytopenia in the first 30 days after ide-cel infusion (46% v 31.5%; p=0.064) and were more likely to receive a thrombopoietin (TPO) agonist (27% v 12%; p=0.017).

Conclusions:

This multicenter retrospective study characterizes a large cohort of patients who received a prior BCMA-TT before treatment with ide-cel, which is associated with inferior PFS and less likelihood of attaining both an overall response and best response of ≥CR. There was a trend towards worse efficacy outcomes for patients who received ide-cel < 6 months after their prior BCMA-TT, and the timing of ide-cel infusion after prior BCMA-TT warrants further investigation.

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

*signifies non-member of ASH