Infectious Complications in Patients Treated with Idecabtagene Vicleucel for Relapsed and Refractory Multiple Myeloma

Introduction: Chimeric antigen receptor (CAR) T-cell therapy is a novel adoptive immunotherapy utilizing autologous T cells expressing synthetic fusion proteins that target specific antitumor antigens. Over recent years, novel CAR T-cell constructs have shown efficacy for the treatment of hematologic malignancies. The B-cell maturation antigen (BCMA)-directed CAR T-cell product idecabtagene vicleucel (ide-cel) is the first approved CAR T-cell therapy for the treatment of multiple myeloma (MM). While ide-cel represents an important advance in MM treatment, it is critical to better characterize the risk of infectious diseases following this novel therapy. Methods: We investigated infectious complications in 27 (CRB-401, n/62; KarMMa, n/128) adult patients who received ide-cel for relapsed and refractory MM at two institutions. Patients were enrolled in an open label, multi-site Phase 1 or 2 clinical trial (NCT02658929; NCT03361748) evaluating the safety and efficacy of ide-cel. All participants received a 3-day cycle of lymphodepleting chemotherapy with fludarabine and cyclophosphamide 5 days prior to infusion and ide-cel was administered at target doses of 150×10 6 to 450×10 6 CAR-positive T cells. All patients but one received antiviral prophylaxis with val/acyclovir or famciclovir. Seventeen patients received pneumocystis prophylaxis with atovaquone or trimethoprim-sulfamethoxazole. Only 2 patients received antibacterial prophylaxis with levofloxacin and no patients received antifungal prophylaxis. Infections were retrospectively identified from day of cell infusion (day 0) up to day 100 after infusion. Infections were reported if patients experienced symptoms with a microbiologic or histopathologic diagnosis, or for symptomatic site-specific infections in conjunction with radiographic or exam findings and treatment with systemic antimicrobials. Infection severity was determined using the Blood and Marrow Transplant Clinical Trials Network criteria. Cytokine release syndrome (CRS) events were graded according to the Lee criteria. Patients were censored on date of disease relapse, the last day of the study period, or death. Results: Median age was 59 (range 41 - 79), 56% were males. Patients had received a median of 6 previous antimyeloma regimens (range 3 - 10); and 74% had undergone prior autologous hematopoietic cell transplantation. Following infusion of cells, 24 patients (89%) developed CRS with 54% of those receiving ≥ 1 dose of tocilizumab and 17%