Safety and Efficacy Outcomes for Patients with High-Risk Multiple Myeloma Receiving Idecabtagene Vicleucel: The MD Anderson Experience

• Published in: Blood 2023-11, Vol.142 (Supplement 1), p.4712-4712
• Main Authors: Pasvolsky, Oren, Hildebrandt, Michelle, Subramanian, Naveen, Ferreri, Christopher, Lee, Hans C., Manasanch, Elisabet E., Thomas, Sheeba K., Weber, Donna M., Gaballa, Mahmoud, Dillard, Christen, Becnel, Melody, Hosing, Chitra, Lin, Pei, Amini, Behrang, Qazilbash, Muzaffar H., Kalariya, Nilesh, Orlowski, Robert Z., Patel, Krina K.
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2023-187854

Background: There is a paucity of data regarding the impact of high-risk features on the efficacy and safety of B-cell maturation antigen (BCMA)-directed autologous chimeric antigen receptor (CAR)-T therapy in patients with multiple myeloma (MM). Methods: In this retrospective single-center study we included all MM patients who received idecabtagene vicleucel (ide-cel) between 12/2019-10/2022, either in the setting of a clinical trial (i.e. KarMMa-2 and KarMMa-3) or as a standard of care (SOC). We evaluated the impact of high-risk disease features on the efficacy and safety outcomes. Patients with high-risk MM (HRMM) were defined as having at least one of the following: high-risk cytogenetic abnormalities prior to CAR-T infusion (deletion 17p, translocation (t)(4:14), t(14:16) or 1q gain/amplification (1q+)), extramedullary disease (EMD), plasma cell leukemia and Revised International Staging System (R-ISS) stage 3. Minimal residual disease (MRD) was evaluated using 8-color next-generation flow cytometry (NGF), with a sensitivity of 1/10-5 cells (0.001%) based on the acquisition and analysis of at least 2 million events. Efficacy outcomes included response rates, progression free survival (PFS) and overall survival (OS). Safety outcomes included incidence/grade of cytokine release syndrome (CRS), Immune effector cell-associated neurotoxicity syndrome (ICANS), hematological toxicity and infections. Results: A total of 74 patients were included in our analysis, 49 received SOC ide-cel and 25 were treated on clinical trial. The median age was 65.3 (range 37.9-90.3) years, and 49 patients (66%) were male. Median number of previous lines of therapy was 6 (range 1-18). The HRMM group included 52 patients (70%), and the most prevalent high-risk features were high-risk cytogenetic abnormalities (43%, most often 1q+ (n=26, 81%), followed by del17p (n=17, 33%), t(4:14) (n=9, 17%) and t(14:16) (n=4, 8%)) and EMD (19%). Seventy five percent of patients who received SOC ide-cel had HRMM compared to 25% of those who received ide-cel on clinical trial (p=0.014). Compared to patients with standard-risk MM (SRMM), those with HRMM more often had disease refractory to proteasome inhibitors (p=0.042) or anti-CD38 antibodies (p=0.01), and more often received bridging therapy prior to CAR-T infusion (p=0.021). After bridging therapy, 43% of HRMM patients had progressive disease, compared to 20% of SRMM patients (p=0.21). Sixty seven percent of the entire cohort received prior B