Abstract A013: 5-year mortality risk in multiple myeloma patients treated with car-t therapy: A comparison of pre-treatment with bendamustine vs. fludarabine and cyclophosphamide

Abstract Introduction Multiple myeloma (MM) ranks as the second most prevalent hematological malignancy, distinguished by the aberrant proliferation of plasma cells, and accounts for 2% of cancer-related mortalities in the United States. Despite the advent of immunomodulatory drugs, proteasome inhibitors, histone deacetylase inhibitors, and monoclonal antibodies, MM remains largely incurable, particularly among high-risk patients who do not respond favorably to existing treatment modalities. A notably promising immunotherapeutic approach is Chimeric Antigen Receptor (CAR) T-cell therapy. Lymphodepletion preceding CAR-T therapy establishes a favorable immune and cytokine environment for CAR-T cell expansion and enhanced cytotoxic effect, thereby enhancing therapeutic efficacy. The combination of fludarabine and cyclophosphamide (Flu/Cy) or bendamustine is commonly employed for lymphodepletion. In this study, we compare the mortality risk post-CAR-T treatment in MM patients pre-treated with either Flu/Cy or bendamustine. MethodsWe conducted a retrospective cohort study utilizing de-identified patient data from the TriNetX platform, a comprehensive electronic health records system consisting of 128 healthcare systems and more than 151 million patients' clinical records globally. Risk of mortality was assessed among MM patients receiving Flu/Cy (Cohort A) compared to bendamustine (Cohort B) therapy. Propensity score matching was utilized to balance baseline characteristics between the cohorts, including age, sex, ethnicity, and comorbidities. ResultsFive years mortality risk among Cohort A was 26.7% (N=105, patients with the outcome = 28) compared to 48.6% for Cohort B (N=105, patients with the outcome = 51), p< 0.0001, risk ratio= 0.549 (CI 95% (0.378 , 0.797)). DiscussionOur findings revealed increased mortality risk among MM patients who received bendamustine therapy compared to fludarabine/cyclophosphamide prior CAR-T therapy. Bendamustine, ist known for its lymphotoxic effects, can impair T-cell function and reduce T-cell numbers. Studies have shown that patients who receive bendamustine prior to CAR T-cell therapy may face less favorable outcomes. Specifically, these patients tend to have lower absolute lymphocyte counts, including CD3+ cells and platelets, and experience reduced CAR T-cell expansion. Additionally, they are more likely to suffer from relapse and exhibit worse progression-free survival (PFS) compared to those not treated with bendamustine. A recent study by Lacoboni et al., reported treatment with bendamustine as an independent factor for poorer outcome of CAR-T therapy in patients with large B-cell lymphoma. Citation Format: Allen Seylani, Assal Sadighian, Sharanya Kumar, Yohannes Haile. 5-year mortality risk in multiple myeloma patients treated with car-t therapy: A comparison of pre-treatment with bendamustine vs. fludarabine and cyclophosphamide [abstract]. In: Proceedings of the AACR IO Conference: Discovery and Innovation in Cancer Immunology: Revolutionizing Treatment through Immunotherapy; 2025 Feb 23-26; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Immunol Res 2025;13(2 Suppl):Abstract nr A013.