Abstracts Clinical Lymphoma, Myeloma & Leukemia September 2023 S528 of Texas, Houston, USA. 5IRCCS Azienda Ospedaliero-Universitaria di Bologna, Seràgnoli Institute of Hematology, Bologna University School of Medicine, Bologna, Italy. 6Winship Cancer Institute of Emory University, Atlanta, USA. 7CHU Lille, Université de Lille, Lille, France. 8University of Wisconsin Carbone Cancer Center, Madison, USA. 9University of Alabama at Birmingham, Birmingham, USA. 10Washington University School of Medicine in St. Louis, Saint Louis, USA. 11Arnie Charbonneau Cancer Institute, University of Calgary, Calgary, Canada. 12University Hospital of Nantes, Nantes, France. 13Northside Hospital Cancer Institute, Atlanta, USA. 14Universitaire Ziekenhuizen, Leuven, Belgium. 15Sarah Cannon Cancer Center and Tennessee Oncology, Nashville, USA. 162seventy bio, Cambridge, USA. 17Bristol Myers Squibb, Princeton, USA. 18Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, United Kingdom. 19Clínica Universidad de Navarra, Pamplona, Spain Context: Patients with RRMM who are TCE to immunomodulatory (IMiD®) agents, proteasome inhibitors (PIs), and antiCD38 monoclonal antibodies have poor survival outcomes. Ide-cel demonstrated deep durable responses in heavily pretreated TCE RRMM. Design: KarMMa-3 (NCT03651128), an international, open-label, RCT, enrolled patients with RRMM who received 2–4 prior regimens (refractory to last regimen) including an IMiD agent, PI, and daratumumab. Patients were randomized 2:1 to idecel or standard regimen (investigator choice: DPd, DVd, IRd, Kd, EPd based on prior regimen). Ide-cel was infused at target dose 150-450×106 CAR+ T cells (≤540×106 cells). Primary endpoint: Independent Response Committee (IRC)-assessed progressionfree survival (PFS). Key secondary endpoints: IRC-assessed overall response rate (ORR), overall survival; other: duration of response (DOR), health-related quality of life (QOL), pharmacokinetics, safety. Efficacy assessed per ITT. Results: Of 386 patients (ide-cel n=254, standard regimens n=132), 225 received ide-cel (median dose 445×106 chimeric antigen receptor [CAR]+ T cells) and 126 received standard regimens. Baseline characteristics (median age [63y], median time since diagnosis [4.1y], median prior therapies [3], high-risk cytogenetics [44%], triple-class [66%] and daratumumab [95%] refractoriness) were generally balanced. Median follow-up from randomization to data cutoff was 18.6 mo. Ide-cel significantly improved PFS (median 13.3 vs 4.4 mo; HR 0.49; P<0.001) and ORR (71% vs 42%; P<0.001) versus standard regimens, with deeper (complete response 39% vs 5%), more durable responses (median DOR 14.8 vs 9.7 mo). PFS and ORR ide-cel benefit were consistent across multiple subgroups. Post–ide-cel infusion, CAR+ T cells underwent rapid multi-log expansion (median 11d to maximum expansion). Adverse events in treated population (ide-cel vs standard regimens): grade 3/4, 93% versus 75%; grade 5, 14% versus 6%; grade 5 treatment-related, 3% versus 1%. Cytokine release syndrome occurred in 88% of ide-cel–treated patients (grade 3/4, 4%); investigator-identified neurotoxicity in 15% of patients (grade 3/4, 3%). Ide-cel demonstrated clinically meaningful improvements in patient-reported outcomes (symptoms, functioning, QOL) versus standard regimens. Conclusion: In early relapse TCE RRMM, idecel significantly improved PFS and ORR, with deep and durable responses versus standard regimens. Toxicity profile was consistent with prior studies. Previous Presentation: ASTCT 2023 (https:// tandem.confex.com/tandem/2023/meetingapp.cgi/Paper/22374). Funding: 2seventy bio and Celgene, a Bristol-Myers Squibb company. Keywords: CT, idecabtagene vicleucel, relapsed and refractory multiple myeloma, Phase III randomized controlled trial, CAR T-cell therapy, progression-free survival CT-359 Trends of BCMA Re‑emergence Post Ide‑cel and Cilta‑cel in Myeloma Aliya Rashid DO, MPH1,2, William Wesson MPH3, Wei Cui MD4, Razan Mansour MD1,2, Muhammad Umair Mushtaq MD2,5, Rajat Bansal MD5, Ramesh Balusu Ph.D.5, Forat Lutfi MD5, Sunil Abhyankar MD5, Leyla Shune MD2,5, Joseph McGuirk DO5, Jenny Ouchveridze MD5, Al-Ola Abdallah MD2,5, Nausheen Ahmed MD2,5 1Department of Internal Medicine, University of Kansas Medical Center, Kansas City, USA. 2US Myeloma Innovations Research Collaborative (USMIRC), Westwood, Kansas, USA. 3University of Kansas School of Medicine, Kansas City, USA. 4Department of Pathology, University of Kansas Medical Center, Kansas City, USA. 5Division of Hematologic Malignancies & Cellular Therapeutics, University of Kansas Cancer Center, Westwood, Kansas, USA Context: The outcomes of patients (pts) with triple and pentaclass relapsed refractory multiple myeloma (RRMM) are poor. B-cell maturation antigen (BCMA) chimeric antigen receptor T-cell (CAR T) therapy in RRMM has been approved since March 2021. Early re-emergence of soluble BCMA may be a prognosticator for clinical relapse. Objective: The objective is to trend re-emergence of BCMA at 3 months and 6 months using multiparameter flow cytometry (MFC) from bone marrow (BM) aspirate or biopsy to compare outcomes between BCMA CAR T products. Design: The study is a prospective cohort study that includes RRMM patients who received BCMA CAR T at the University of Kansas Health System over the last 2 years, followed at intervals of 3 months. Setting: The study setting was conducted at the University of Kansas Health System requiring both inpatient and outpatient care. Participants: A total of 56 pts who received BCMA CAR T therapy recipients for RRMM at the University of Kansas Health System between May 2021 and May 2023 were included. Those with less than 3 months of follow-up were excluded from the analysis. Interventions: All patients had standard procedure of BM evaluation at 1 3 and 6 months, and 1 year. Eight-color MFC was performed on the BM specimens. Main Outcome Measures: Responses were evaluated using the International Myeloma Working Group criteria. BCMA re-emergence was defined as BCMA greater than nadir on either polyclonal or monoclonal BM plasma cells. Results: Fifty-six pts were included in the analysis, of which 38 received ide-cel and 18 received cilta-cel. A greater proportion of ide-cel patients had cumulative re-emergence of BCMA within 12 months post-CAR T compared to cilta-cel patients (58% vs 17%, P=0.004). However, the possible limitation is that there was a significant difference in follow-up time between ide-cel and cilta-cel patients that could explain this difference (11 vs 4 months, P=0.004). Conclusion: There are possible differences in re-emergence of BCMA in different BCMA-CAR T products. This is an early observation and we need
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