Risk of second primary hematological malignancy post CAR-T cell therapy in relapsed/refractory multiple myeloma: Propensity-matched analysis using TriNetX database.

Abstract

7523 Background: The Food and Drug Administration (FDA) issued a black box warning regarding the risk of T-cell lymphoma post CAR-T cell therapy has drawn global attention yet comprehensive profiling of Second Primary Malignancies is lacking in this group of patients. To address this knowledge gap, we aimed to comprehensively elucidate the current landscape of SPMs post CAR-T therapy in patients with multiple myeloma using real-world, large-scale data from TrinetX. Such efforts will be instrumental in guiding the lifelong safety monitoring of CAR-T products in the future. Methods: We conducted a retrospective study that included adult patients with RRMM who received CART cell therapy versus those who did not receive CART cell therapy using the TrinetX database network, a federated EMR network of more than 117 million de-identified patients. The outcomes of interest were assessing Second Primary Hematological Malignancies. Propensity matching analysis was done to assess the risk of SPM post-CART cell therapy. Results: A total of 803 RRMM patients received CAR-T cell therapy and 62038 RRMM patients without CART cell therapy were identified. Before matching the median follow-up was 12 months in the CART group versus 33.2 months in the non-CART group. After propensity matching analysis at a median follow-up of 12 months in the CART group and 34.4 months in the non-CART group, it was found that there was no significant increase in the risk of SPM in the CART group. (Table 1) The most common SPM remains to be AML (5%) followed by MDS (3.5%). No cases of Adult T-cell leukemia/lymphoma were detected. Conclusions: This real-world study shows no increased risk of second primary malignancies (SPM) following CAR T-cell therapy. Although we may have underestimated the cases if they were not admitted, and also due to limited follow-up which might not capture the late-onset SPMs. The group’s next step is to re-evaluate the risk of SPM in this subgroup at five years of follow-up. Hematological SPM post CART cell therapy after propensity matching analysis. Type of SPM RRMM post CART (n=800) RRMM without CART (n=796) Follicular lymphoma 0% 10 (1.25%) Mantle cell lymphoma 0% 0 % DLBCL 10 (1.25%) 10 (1.25%) Hairy cell leukemia 0 % 0% CLL 10 (1.25%) 10 (1.25%) Hodgkin lymphoma 0 % 10 (1.25%) Adult T cell leukemia/lymphoma 0% 0% Mature T/NK cell lymphoma 0% 10 (1.25%) AML 40 (5%) 32 (4.0%) MDS 28 (3.5%) 21 (2.6%) ALL 13 (1.62%) 20 (2.5%) MDS: Myelodysplastic syndrome; AML: Acute myelogenous leukemia; ALL: Acute lymphoblastic leukemia; DLBCL: Diffuse Large B Cell Lymphoma; CLL: Chronic Lymphocytic Leukemia; NK: Natural Killer cells; RRMM: Relapse/Refractory Multiple Myeloma; CART: Chimeric Antigen Receptor T cell therapy; SPM: Second primary malignancy.