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4712 Safety and Efficacy Outcomes for Patients with High-Risk Multiple Myeloma Receiving Idecabtagene Vicleucel: The MD Anderson Experience

Program: Oral and Poster Abstracts
Session: 652. Multiple Myeloma: Clinical and Epidemiological: Poster III
Hematology Disease Topics & Pathways:
Biological therapies, Chimeric Antigen Receptor (CAR)-T Cell Therapies, Plasma Cell Disorders, Diseases, Therapies, Lymphoid Malignancies
Monday, December 11, 2023, 6:00 PM-8:00 PM

Oren Pasvolsky, MD1*, Michelle Hildebrandt, PhD2, Naveen Subramanian, MD3, Christopher Ferreri, MD4*, Hans Lee, MD5, Elisabet E. Manasanch, MD6*, Sheeba K. Thomas, MD6, Donna M. Weber, MD6, Mahmoud Gaballa, MD6, Christen Dillard, MD2*, Melody Becnel, MD7, Chitra Hosing, MD1, Pei Lin, MD, DM, MDPC8, Behrang Amini, MD, PhD9*, Muzaffar H. Qazilbash, MD1, Nilesh Kalariya, PhD, RN6*, Robert Z. Orlowski, MD, PhD10 and Krina K. Patel, MD, MSc11

1Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
2The University of Texas MD Anderson Cancer Center, Houston, TX
3Department of Internal Medicine, The University of Texas Health Sciences Center at Houston, Austin, TX
4MD Anderson Cancer Center, Houston
5Department of Lymphoma/Myeloma, MD Anderson Cancer Center, Houston, TX
6Department of Lymphoma & Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX
7Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, Houston
8Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX
9Department of Musculoskeletal Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX
10Department of Experimental Therapeutics, MD Anderson Cancer Center, Houston, TX
11University of Texas MD Anderson Cancer Center, Houston, TX

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 BCMA-directed therapy before ide-cel, without a significant difference between the two risk groups (p=0.80) (Table 1).

For the entire cohort, overall response rate was 85%, and 51% achieved ≥CR at best response. There was no significant difference between the HRMM and SRMM groups in response rates or in rates of MRD negativity at day 30 and at 3/6/9 months after CAR-T infusion, yet fewer HRMM had MRD negativity at 12 months after CAR-T (50% vs. 100% of evaluable patients, p=0.019). The 6-months PFS for the HRMM group and the SRMM group was 64% and 81%, respectively (p=0.11) (Figure 1A), and the 6-months OS was 80% and 90%, respectively (p=0.067) (Figure 1B);

Thirty-nine patients in the HRMM group developed CRS (83% of evaluable patients), including one grade 3 and one grade 5 CRS, compared to 15 (75%, p=0.65) in the SRMM group (all grade <3). Eight patients in the HRMM group developed ICANS (17%), including two grade 4 ICANS, compared to 3 (15%, p=0.93) in the SRMM group (all grade <3). We did not observe a difference in rates of neutropenia (p=0.63), anemia (p=0.75) or thrombocytopenia (p=0.53) by day 30, and also not in the rates of infection (p=0.16) between the two groups.

In multivariate analysis on the entire cohort, receiving <4 prior lines of therapy (HR 0.06, 95% CI 0.004-0.71, p=0.026) and ECOG≤2 (HR 0.07, 95% CI 0.08-0.53, p=0.01) were associated with superior OS.

Conclusions: Patients with HRMM receiving ide-cel had mostly comparable response rates compared to those with SRMM. HRMM patients had numerically worse PFS and OS compared to patients with SRMM, though not reaching statistical significance. Overall rates of CRS/ICANS were comparable between the two groups, yet only patients with HRMM had grade ≥3 of these complications. Patients who received ide-cel after less than four previous lines of therapy had better overall survival.

Disclosures: Lee: Celgene: Consultancy; Monte Rosa Therapeutics: Consultancy; Regeneron: Consultancy, Research Funding; Pfizer: Consultancy; GlaxoSmithKline: Consultancy, Research Funding; Amgen: Research Funding; Sanofi: Consultancy; Allogene Thereapeutics: Consultancy; Takeda Pharmaceuticals: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Genentech: Consultancy; Bristol Myers Squibb: Consultancy, Research Funding; AbbVie: Consultancy. Thomas: Bristol Myers Squibb, Janssen Pharma Genentech, X4 pharma, Cellectar Biosciences, Ascentage Pharma: Research Funding; Abbvie, Cellectar Biosciences: Consultancy; Genentech: Research Funding; X4 pharma: Research Funding; Cellectar Biosciences: Research Funding; Janssen Pharma: Research Funding; Ascentage Pharma: Research Funding; Cellectar Biosciences: Consultancy. Gaballa: Boxer Capital, LLC: Consultancy. Qazilbash: Angiocrine: Research Funding; Janssen: Research Funding; Amgen: Research Funding; NexImmune: Research Funding; Bioline: Other: Advisory board. Orlowski: BMS/Celgene Corporation, CARsgen Therapeutics, Exelixis Inc., Heidelberg Pharma, Janssen Biotech Inc., Sanofi/Genzyme, Takeda Pharmaceuticals USA Inc.: Other: Clinical Research Funding, Research Funding; AbbVie, Adaptive Biotech, Asylia Therapeutics, Inc., BioTheryX, Bristol-Myers Squibb Pharmaceuticals, Karyopharm Therapeutics, Meridian Therapeutics, Monte Rosa Therapeutics, Nanjing IASO Biotherapeutics, Neoleukin Corporation, Oncopeptides AB, Pfizer, In: Consultancy, Honoraria; Asylia Therapeutics, BioTheryX Inc., Heidelberg Pharma: Other: Laboratory Research Funding, Research Funding; Asylia Therapeutics: Current equity holder in private company, Patents & Royalties. Patel: AbbVie; Allogene Therapeutics, Inc.; Arcellx; Bristol Myers Squibb/Celgene Corporation; Cellectis; Janssen Pharmaceuticals, Inc.; Nektar Therapeutic; Poseida Therapeutics; Precision BioSciences, Inc.; and Takeda Pharmaceuticals U.S.A., Inc.: Research Funding; Takeda: Consultancy; AbbVie; Arcellx, AstraZeneca; Bristol Myers Squibb/Celgene Corporation; Caribou Science; Cellectis; Curio Bioscience; Genentech; Janssen Pharmaceuticals, Inc.; Karyopharm; Legend Biotech; Merck & Co., Inc.; Oncopeptides; Pfizer; Precision BioSciences: Consultancy.

*signifies non-member of ASH