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2405 Chimeric Antigen Receptor T-Cell Therapy for Relapsed/Refractory Multiple Myeloma: A Real-World Experience

Program: Oral and Poster Abstracts
Session: 907. Outcomes Research: Plasma Cell Disorders: Poster I
Hematology Disease Topics & Pathways:
Chimeric Antigen Receptor (CAR)-T Cell Therapies, Biological therapies, Treatment Considerations
Saturday, December 7, 2024, 5:30 PM-7:30 PM

Bhavesh Mohan Lal, MD1, Toshali Pandey2*, Marah Alzubi3*, Jawad Alrawabdeh3*, John D Shaughnessy, Jr, PhD4*, Fenghuang Zhan, MD5, Eric Siegel6*, Carolina Schinke, MD5, Sharmilan Thanendrarajan, MD7, Maurizio Zangari, MD5, Frits van Rhee, MD, PhD5 and Samer Al Hadidi, MD, MSc7

1University of Arkansas for Medical Sciences, Little Rock, Little Rock, AR
2University of Arkansas for Medical Sciences, Little Rock
3University of Jordan, Amman, Jordan
4Myeloma Center, Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical sciences, Little Rock, AR
5Myeloma Center, Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, AR
6Department of Biostatistics, University of Arkansas For Medical Sciences, Little Rock, AR
7University of Arkansas for Medical Sciences, Little Rock, AR

Introduction: Chimeric antigen receptor T-cell (CAR T) therapy has revolutionized the treatment of relapsed/refractory multiple myeloma (RRMM). However, in real-world settings, patients face lengthy wait times, and not all who are listed for CAR T-cell therapy receive it.

Methods: In this single-center retrospective observational study performed at the University of Arkansas for Medical Sciences, we analyzed the outcomes for all patients listed for B-cell maturation antigen (BCMA) CAR T-cell therapy for RRMM, including those who did not receive it.

Results: 152 patients with RRMM were listed to receive CAR T-cell therapy on or before November 1, 2023. The median age of the patients at the time of listing was 66 years (range: 33-85 years), with a median of 6 years from initial diagnosis to listing. The patients had a median of 7 (range: 1-15) lines of therapy prior to listing. Patients had a median of two prior autologous stem cell transplants. All the patients had received at least one immunomodulatory drug (IMiD) and proteasome inhibitor, and 143 (93%) patients received anti CD-38 monoclonal antibody. 53 (35%) patients received prior anti-BCMA therapy. At the time of listing, 83 (55%) patients had at least one factor that would exclude them from the KarMMa trial, with prior anti-BCMA therapy being the most common reason.

Out of 152 patients, 72 (47%) completed apheresis, and 70 (46%) patients received CAR T-cell therapy. The remaining 82 patients received alternative treatment regimens. Cyclophosphamide-based regimens and daratumumab-based regimens were the most frequently used regimens in these patients. The two most common reasons for not receiving CAR T-cell therapy while on the waitlist were the need for interval disease control and death, which together comprised 78% of cases. Patients who received CAR T-cell therapy were similar to those who did not receive it, except that the group who received CAR T-cell therapy had a higher number of patients with active disease on PET scans and a lower incidence of del(17p) mutation at the time of listing.

Among patients who received CAR T-cell therapy, the median time from listing to CAR T-cell infusion was 194 (range: 54-691) days. 62 (89%) patients received ide-cel, 7 (10%) patients received cilta-cel, and 1 (1%) patient received investigational BCMA CAR-T. The median duration of follow-up after CAR T-cell infusion was 11.9 months. 62 (89%) patients developed cytokine release syndrome (CRS), with grade III CRS occurring in 3 (4%) patients. Immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 11 (16%) patients, with 1 (1%) patient developing grade III ICANS. Any grade of neutropenia, anemia, and thrombocytopenia occurred in 66 (94%), 68 (97%), and 60 (86%) patients, respectively in the first month after CAR T-cell therapy. 64 (91%) patients had grade 3 or higher neutropenia, 31 (44%) patients had grade 2 or higher anemia, and 45 (64%) patients had grade 3 or higher thrombocytopenia.

Outcomes were calculated in two ways: an ‘intention to treat’ analysis including all patients from the time of listing regardless of CAR T-cell infusion status, and a ‘per treatment’ analysis calculated from the date the patient received a treatment to progression/death (PFS) or death (OS). The overall response rate (ORR) for all patients listed was 48%. Patients who received CAR T-cell therapy had a higher ORR compared to patients who did not receive CAR T-cell therapy and received an alternative regimen (63% vs. 39%). In the per-treatment analysis, the median progression-free survival (PFS) and overall survival (OS) for patients who received CAR-T were 12.8 months and OS not reached, respectively, compared to a median PFS of 5.4 months and OS of 15.4 months in patients who did not receive CAR T-cell therapy and received alternative treatment regimens.

Conclusions: In conclusion, more than half of the patients listed for CAR T-cell therapy did not receive it. There was an association between receiving CAR T-cell therapy and improved PFS and OS compared to those who did not receive the CAR T-cell therapy. This real-world analysis uniquely follows an intent-to-treat CAR T cohort, including patients who did not receive CAR T-cell therapy. Previous real-world studies have focused on intent-to-manufacture cohorts, lacking a comparison with patients having similar baseline disease who received contemporary alternative therapies instead of CAR T-cell therapy.

Disclosures: Schinke: Arcellx: Consultancy; Pfizer: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; OncLive: Honoraria; Cancer Network: Honoraria. Zangari: Karyopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen Pharmaceuticals, Inc: Consultancy, Membership on an entity's Board of Directors or advisory committees. van Rhee: Takeda: Consultancy; Adicet Bio: Membership on an entity's Board of Directors or advisory committees; Secura Bio: Membership on an entity's Board of Directors or advisory committees; Castleman Disease Collaborative Network: Membership on an entity's Board of Directors or advisory committees; Kite Pharma: Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Consultancy, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees; EUSA Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol Myers Squibb: Research Funding. Al Hadidi: Sanofi: Consultancy; Pfizer: Consultancy; Janssen: Consultancy.

*signifies non-member of ASH