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1862 Outcomes of Patients Who Are BCMA (B-cell maturation Antigen) Directed Therapy (BDT) Exposed Vs BCMA Naïve in Penta-Relapsed Refractory Multiple Myeloma (RRMM)

Program: Oral and Poster Abstracts
Session: 652. Multiple Myeloma and Plasma Cell Dyscrasias: Clinical and Epidemiological: Poster I
Hematology Disease Topics & Pathways:
Biological therapies, Antibody Therapy, Bispecific Antibody Therapy, Plasma Cell Disorders, Chimeric Antigen Receptor (CAR)-T Cell Therapies, Combination therapy, Checkpoint Inhibitor, drug development, Diseases, Gene Therapy, drug-drug interactions, Therapies, Immunotherapy, therapy sequence, Lymphoid Malignancies, Infusion, Monoclonal Antibody Therapy, Natural Killer (NK) Cell Therapies, Transfusion, Transplantation, Minimal Residual Disease
Saturday, December 10, 2022, 5:30 PM-7:30 PM

Aytaj Mammadzadeh1*, Fulei Peng, MD2*, Shebli Atrash, MD3,4, Hamza Hashmi, MD3,5, Meera Mohan, MD3,6, Omar Alkharabsheh, MBBS3,7, Aimaz Afrough, MD3,8, Wei Cui, MD3,9*, Zahra Mahmoudjafari, PhD3,10* and Al-Ola Abdallah, MD11,12

1Division of Hematology, Mayo Clinic, Rochester, MN
2Department of Internal Medicine, Mercy St. Louis Hospital, St. Louis, MO
3US Myeloma Research Innovations Research Collaborative (USMIRC), Westwood, KS
4Department of Hematologic Oncology and Blood Disorders, Levine Cancer Institute, Atrium Health, Charlotte, NC
5Department of Hematology/Medical Oncology, Medical University of South Carolina, Charleston, SC
6Medical College of Wisconsin, Milwaukee, WI
7Division of Hematology/Oncology, University of South Alabama Mitchell Cancer Institute, Mobile, AL
8Division of Hematologic Malignancies and Cellular Therapy, Dept of Internal Medicine, Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX
9University of Kansas Medical Center, Kansas City, KS
10Division of Hematologic Malignancies & Cellular Therapeutics, University of Kansas Medical Center, Kansas City, KS
11Division of Hematologic Malignancies & Cellular Therapeutics, University of Kansas Medical Center, Westwood, KS
12US Myeloma Innovations Research Collaborative (USMIRC), Westwood, KS

Introduction: Treatment options for multiple myeloma (MM) have evolved in recent years, with introduction of novel therapeutic agents such as proteasome inhibitors (PI), anti-CD-38 monoclonal-antibodies (MoAb), and immunomodulatory drugs (IMiDs) that have significantly improved survival in patients with MM, however, MM remains an incurable disease characterized by a relapse-remission pattern. Despite advances in treatment, outcomes remain poor for those who are penta-RRMM (refractory to two different IMiDs: lenalidomide and pomalidomide, two different PI's: bortezomib and carfilzomib, and a CD-38 MoAb: daratumumab or isatuximab), with a historical median survival of 5.6 months. Recently B-cell maturation Antigen (BCMA)- directed therapy (BDT) is being increasingly used in heavily treated RRMM. This is a retrospective analysis, evaluating survival outcome of penta-RRMM pts who were treated with BDT (BCMA exposed) and comparing these outcomes with those who did not receive BDT (BCMA naïve)

Patients & Methods: Seventy-eight RRMM pts were identified as penta-RRMM at University of Kansas Health System between January 2015 to July 2022 and had electronic medical records (EMR) reviewed retrospectively. All patients identified met the inclusion criteria for penta-RRMM. Descriptive analyses were performed on available data obtained from patient characteristics. Survival curves were generated using the Kaplan-Maier method. Responses were evaluated using the International Myeloma Working group (IMWG) criteria. Baseline characteristics including high-risk cytogenetics, disease stage, lines of therapy (LOT), treatment response, and survival outcomes were obtained retrospectively from EMR. High-risk cytogenetics were defined as the presence of t(4;14), t(14;16) or del 17p; 1q21 gain or amplification; t(6;14); t(14;20).

Results: The median age was 65 years, 44 (56%) patients had IgG isotype, 29 (37 %) had R-ISS stage III disease, 63 (81%) had high-risk cytogenetics, and 45 (58%) had extramedullary disease (EMD). The median number of previous lines of therapy for all patients was 8 (3-15), while the median LOT prior to reaching penta-refractory state was 5 (3-12), with a median of time from diagnosis to penta-refractory state 60 (4-176) months. Patient characteristics are summarized in Table 1. With a median follow-up (IQR) of 13 (4.9;29.5) months, median overall survival (OS) was 12 months (Figure 1).

Amongst this group of penta-RRMM patients 43 (55%) were identified as BCMA exposed vs 35 (45%) who were BCMA naïve. Type of BDT patients received included: belantamab mafadotin 15 (35%), Chimeric Antigen Receptor T cell therapy (CAR-T) 9 (21%), BCMA MoAb 6 (14%), and Bispecific T-cell engager (BiTE) 2 (5%). Eleven (25%) patients received more than one different BDT. The median time from initial diagnosis to penta refractory state in BCMA exposed vs BCMA naïve pts were 66 (4-176) and 48 (14-135) months, respectively. Median OS for BCMA exposed vs BCMA naïve pts were 17 vs 6 months, respectively (95% CI (0.18-0.51), p<0.0001). Common causes of mortality in all patients with penta-RRMM were disease progression, infection/sepsis, and secondary primary cancers in 89%, 6% and 5%, respectively.

Conclusion: Penta-RRMM patients have significantly worse outcomes, though our retrospective analysis indicated a significant survival benefit using BDT for penta-RRMM. Prospective studies are required to confirm these findings. Penta-RRMM represents a significant challenge with an unmet need for more therapeutic options.

Disclosures: Atrash: Celgene: Honoraria, Speakers Bureau; GSK: Honoraria, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Sanofi: Honoraria, Speakers Bureau; Takeda: Honoraria; Amgen: Research Funding. Hashmi: JANSSEN: Consultancy; KARYOPHARM: Speakers Bureau; GSK: Speakers Bureau; Sanofi: Consultancy, Speakers Bureau; BMS: Consultancy. Mohan: Takeda: Research Funding; GSK: Research Funding; BMS/Celgene: Research Funding; Novartis: Research Funding. Alkharabsheh: National Community Oncology Dispensing Association, Inc: Consultancy; Genentech: Consultancy; Incyte: Consultancy; AstraZeneca: Consultancy; Agios: Consultancy; Amgen: Consultancy. Mahmoudjafari: Incyte: Membership on an entity's Board of Directors or advisory committees; Merk: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Omeros: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

*signifies non-member of ASH