Real-world impact of bridging therapy on outcomes of ide-cel for myeloma in the U.S. Myeloma Immunotherapy Consortium
Authors: Aimaz Afrough, Hamza Hashmi, Doris K. Hansen, Surbhi Sidana, Chul Ahn, Lauren C. Peres, Danai Dima, Ciara L. Freeman, Omar Castaneda Puglianini, Mehmet H. Kocoglu, Shebli Atrash, Peter M. Voorhees, Leyla Shune, Joseph P. McGuirk, Gary Simmons, Douglas W. Sborov, James A. Davis, Gurbakhash Kaur, Aishwarya Sannareddy, Christopher J. Ferreri, Mahmoud R. Gaballa, Scott Goldsmith, Omar Nadeem, Shonali Midha, Charlotte B. Wagner, Frederick L. Locke, Krina K. Patel, Jack Khouri, Larry D. Anderson, Yi Lin
Journal: Blood Cancer Journal (2024)

Idecabtagene vicleucel (ide-cel) the first FDA-approved gene therapy for relapsed refractory multiple myeloma (RRMM).However, its administration presents challenges in logistical management, selecting bridging therapy (BT), and customizing T-cell manufacturing, a complex process spanning several weeks [1].In the KarMMa trial, BT was allowed but limited to specific prior drug classes (e.g., dexamethasone, cyclophosphamide (Cy), daratumumab, carfilzomib, bortezomib, or pomalidomide) [2].This study delves into the impact of different BT on outcomes for RRMM patients undergoing standard of care (SOC) ide-cel treatment, aiming to clarify their role in CAR T therapy outcomes.This retrospective multicenter study observed RRMM patients receiving ide-cel treatment at 11 U.S. medical centers within the U.S. Myeloma Immunotherapy Consortium.All RRMM patients treated with ide-cel from 5/2021 to 5/2022, were included.BT was defined as systemic treatment between leukapheresis and CAR-T infusion, categorized into: Selinexor (Selinexor-containing regimens); alkylator (alkylator-based); PI combos (sole or combined proteasome inhibitor (PI) therapy); IMiD +/-mAb combos (steroids with/without immunomodulatory (IMiDs) and/or Monoclonal Antibodies (mAb).High-risk cytogenetics included del (17p), t(4;14), and t(14;16) pre-CAR-T.Cytokine Release Syndrome (CRS) and Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) were graded by American Society for Transplantation and Cellular Therapy criteria [3].Hematologic toxicity was assessed using Common Terminology Criteria for Adverse Events version 5.0 [4].Disease response followed the revised International Myeloma Working Group criteria [5].Subgroup comparisons employed chi-square/Fisher's exact tests for categorical, t-tests/ANOVA for continuous variables.Survival analysis used Kaplan-Meier/Cox proportional hazards model.Stepwise Cox regression identified significant variables associated with overall survival (OS) and progression free survival (PFS), based on p-values < 0.2 from initial analysis.SAS (v9.4) and IBM SPSS (v29.0)conducted all statistical analyses.Of 214 ide-cel patients, 170 (79%) underwent BT, encompassing 12% Selinexor, 45% alkylator, 15% PI combos, 18% IMiD +/-mAb combos, and 11% other therapies (e.g., belantamab mafodotin, focal radiation).Forty-four patients (21%) did not receive BT (no-BT).The median BT duration was 1 month (range, 1-7).While most had 1-2 months, one patient had 7 months with 4 treatments.BT patients showed poorer eastern Cooperative Oncology Group Performance Status (ECOG), higher Revised International Staging System (R-ISS) (2-3), elevated ferritin ( > 300 ng/mL), and C-reactive protein (CRP) ( > 5 mg/L) at lymphodepleting chemotherapy (Supplementary 1).IMiD +/-mAb combos had less extramedullary disease (EMD) (p = 0.052),