Real-life experiences with CAR T-cell therapy with idecabtagene vicleucel (ide-cel) for triple-class exposed relapsed/refractory multiple myeloma patients

Abstract

Background Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment landscape of relapsed/refractory multiple myeloma (RRMM), leading to unprecedented responses in this patient population. Idecabtagene vicleucel (ide-cel) has been recently approved for treatment of triple-class exposed RRMM. We report real-life experiences with the commercial use of ide-cel in RRMM patients. Methods We performed a retrospective analysis of the first 16 triple-class exposed RRMM patients treated with ide-cel at a single academic center. We assessed toxicities, response to treatment, CAR T expansion and soluble BCMA (sBCMA) levels. Results We identified 16 consecutive RRMM patients treated with ide-cel between 06–10/2022. Median age was 69 years, 6 (38%) patients had high-risk cytogenetics, 3 (19%) R-ISS stage III, and 5 (31%) extramedullary disease. Median number of previous treatment lines was 6 (3–12). Manufacturing success rate was 88% (6% required second lymphapheresis, 6% received an out-of-specification product). At 3 months, the overall response rate (ORR) was 69% (44% sCR, 6% CR, 19% VGPR). Cytokine release syndrome (CRS) occurred in 15 (94%) patients (88% G1, 6% G2), immune effector-cell associated neurotoxicity syndrome (ICANS) in 1 (6% G1), febrile neutropenia in 11 (69%), and infections in 5 (31%). Prolonged hematologic toxicity occurred in 4/16 (25%) patients. Other non-hematological toxicities were elevated hepatic enzymes (38%), colitis (6%, G3) and DIC (6%, G2). Responses were more frequent in patients with higher CAR T expansion (100% vs 38%), and lack of decrease or plateau of sBCMA levels was typically observed in non-responders. Conclusions We report one of the first cohorts of RRMM treated with commercial ide-cel. The ORR was 69% and safety profile was manageable, but prolonged hematologic toxicity still represents a major challenge. Responses correlated with in vivo CAR T cell expansion, underlining the need of further research to optimize CAR T expansion.

Cellular dynamics following CAR T cell therapy are associated with response and toxicity in relapsed/refractory myeloma

“…In line with the real world analysis by Sanoyan et. al (13), our ow cytometry-based analysis revealed similar phases in BCMA-CAR T celltreated RRMM patients, with a peak expansion around two weeks after infusion and a rapid decline afterwards. In addition, the lack of expansion was accompanied by an absent response and early progression of the disease.…”

“…Our ndings, along with the real world study by Sanoyan et. al (13) support these observations. Similar to the KarMMa trial (10), 81% of our patients developed CRS and 32% of these patients required tocilizumab treatment.…”

“…Hematologic toxicity, characterized by anemia, neutropenia and thrombocytopenia, was observed in all patients, which aligns with the ndings of Sanoyan et. al (13). Additionally, a subgroup of patients had signi cantly reduced cell counts for all three lines even before LDP, and interestingly, all of these patients developed CRS requiring tocilizumab treatment after CAR T cell infusion.…”

CAR-T Cell Therapy Shows Similar Efficacy and Toxicity in Patients With DLBCL Regardless of CNS Involvement

“…6 While an extensive expertise has been gathered in the field of CAR-T cell therapy and B-cell lymphoproliferative malignancies with systemic manifestations, still little is known regarding efficacy and side effects of CAR-T cell therapy in those patients presenting with central nervous system (CNS) disease. [8][9][10][11] r/r DLBCL patients with CNS involvement represent an unmet clinical need. Commonly, high-dose methotrexate (MTX)-based and/or cytarabine (ARA-C)-based polychemotherapy penetrating the blood-brain barrier is administered.…”

“…While an extensive expertise has been gathered in the field of CAR‐T cell therapy and B‐cell lymphoproliferative malignancies with systemic manifestations, still little is known regarding efficacy and side effects of CAR‐T cell therapy in those patients presenting with central nervous system (CNS) disease 8–11 …”