Impact of extramedullary multiple myeloma on outcomes with idecabtagene vicleucel.

person Saurabh Zanwar Division of Hematology, Mayo Clinic, Rochester, MN info_outline Saurabh Zanwar, Surbhi Sidana, Leyla Shune, Omar Alexis Castaneda Puglianini, Oren Pasvolsky, Rebecca Gonzalez, Danai Dima, Aimaz Afrough, Gurbakhash Kaur, James A. Davis, Megan Herr, Hamza Hashmi, Peter A. Forsberg, Douglas W. Sborov, Shambavi Richard, Jack Khouri, Yi Lin, Krina K. Patel, Shaji Kumar, Doris K. Hansen

Authors person Saurabh Zanwar Division of Hematology, Mayo Clinic, Rochester, MN info_outline Saurabh Zanwar, Surbhi Sidana, Leyla Shune, Omar Alexis Castaneda Puglianini, Oren Pasvolsky, Rebecca Gonzalez, Danai Dima, Aimaz Afrough, Gurbakhash Kaur, James A. Davis, Megan Herr, Hamza Hashmi, Peter A. Forsberg, Douglas W. Sborov, Shambavi Richard, Jack Khouri, Yi Lin, Krina K. Patel, Shaji Kumar, Doris K. Hansen Organizations Division of Hematology, Mayo Clinic, Rochester, MN, Stanford University Medical Center, Palo Alto, CA, University of Kansas Medical Center, Kansas City, KS, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, The University of Texas MD Anderson Cancer Center, Houston, TX, Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, UT Southwestern Medical Center, Dallas, TX, Medical University of South Carolina, Charleston, SC, Roswell Park Comprehensive Cancer Center, Buffalo, NY, University of Colorado School of Medicine, Aurora, CO, The University of Utah Huntsman Cancer Institute, Salt Lake City, UT, Icahn School of Medicine at Mount Sinai, New York, NY, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH Abstract Disclosures Research Funding No funding sources reported Background: Idecabtagene vicleucel (Ide-cel) has demonstrated excellent efficacy in patients with relapsed/refractory multiple myeloma (RRMM). However, outcomes in patients with extramedullary disease (EMD) remain to be better characterized. Methods: We included patients from 11 US academic centers, who were evaluated for EMD and were infused with ide-cel between May 2021 and April 2023. Patients with soft tissue or visceral lesions non-contiguous from bony lesions were classified as having true EMD, with paraskeletal disease classified as non-EMD. Disease responses were evaluated using the IMWG criteria. Time-to-event analyses were performed from the date of ide-cel infusion. Results: Among 351 patients with RRMM treated with ide-cel, 84 (24%) had EMD prior to infusion. Median follow-up for the entire cohort was 18.2 months (95% CI: 17-19.3). Baseline characteristics at ide-cel infusion for EMD and non-EMD cohorts are depicted in the table. For the EMD and non-EMD cohorts, the Day 30 objective response rates (ORR) were 58% vs. 69% (p=0.1), Day 30 ≥complete response rates were 16% vs 24% (p=0.11), the Day 90 ORR were 52% vs 82% (p<0.001), and best ORR were 58% vs 82%, respectively. The median progression-free survival (PFS) was 5.3 months (95% CI: 4.1-6.9) for the EMD cohort vs. 11.1 months (95% CI: 9.2-12.6; p<0.0001) for the non-EMD cohort. The median duration of response for EMD among day 30 responders was 6.4 months (95% CI: 5.1-8.4). In a multivariable analysis, EMD was an independent predictor of inferior PFS [hazard ratio 1.8 (95% CI: 1.2-2.5), p<0.001] after adjusting for ECOG status, revised ISS stage, penta-drug refractoriness, elevated ferritin, prior BCMA-directed therapy and use of bridging therapy. Pattern of progression in the EMD cohort (n=68/84) included EMD site only (21%), hematologic only (22%), or both (57%), with comparable PFS for type of progression (p=0.19). The median overall survival (OS) was 14.8 months [95% CI: 9-Not reached (NR)] for EMD and 26.9 months [95% CI: 26.3 vs NR, p=0.006)] for the non-EMD group. Rates of Grade ≥2 cytokine release syndrome or neurotoxicity syndrome were comparable between the two cohorts. Conclusions: Patients with EMD demonstrate significantly inferior Day 90 ORR and presence of EMD is an independent risk factor for inferior PFS. Patient Characteristics Data Available in, n (%) Extramedullary Disease (n=84) No Extramedullary Disease (n=267) P value Age, median (interquartile range), years 351 (100) 62 (55-69) 66 (59-71) 0.02 ECOG 0-1, n (%) 333 (95) 62 (78) 225 (89) 0.02 Revised ISS Stage III, n (%) 256 (73) 11 (23) 42 (21) 0.65 High-Risk Cytogenetics [t(4;14), deletion 17p, t(14;16)], n (%) 308 (88) 20 (29) 79 (33) 0.47 Prior Lines of Therapy, median (interquartile range) 351 (100) 6 (5-8) 6 (5-8) 0.19 Triple Class Refractory, n (%) 351 (100) 74 (88) 215 (81) 0.11 Penta-refractory, n (%) 351 (100) 39 (46) 86 (32) 0.02 Bridging Therapy, n (%) 351 (100) 67 (80) 195 (73) 0.08