Prognostic impact of corticosteroid and tocilizumab use following chimeric antigen receptor T-cell therapy for multiple myeloma.
Bruno Almeida CostaJessica FlynnNoriko NishimuraSean M DevlinTasmin FarzanaSridevi RajeeveDavid J ChungHeather J LandauOscar B LahoudMichael ScordoGunjan L ShahHani HassounKylee H MaclachlanMalin L HultcrantzNeha KordeAlexander M LesokhinUrvi A ShahCarlyn Rose TanSergio A GiraltSaad Z UsmaniKarthik NathSham MailankodyPublished in: Blood cancer journal (2024)
Despite being the mainstay of management for cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), there is limited data regarding the impact of tocilizumab (TCZ) and corticosteroids (CCS) on chimeric antigen receptor (CAR) T-cell efficacy in multiple myeloma (MM). The present study aims to evaluate the prognostic impact of these immunosuppressants in recipients of BCMA- or GPRC5D-directed CAR T cells for relapsed/refractory MM. Our retrospective cohort involved patients treated with commercial or investigational autologous CAR T-cell products at a single institution from March 2017-March 2023. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall response rate (ORR), complete response rate (CRR), and overall survival (OS). In total, 101 patients (91% treated with anti-BCMA CAR T cells and 9% treated with anti-GPRC5D CAR T cells) were analyzed. Within 30 days post-infusion, 34% received CCS and 49% received TCZ for CRS/ICANS management. At a median follow-up of 27.4 months, no significant difference in PFS was observed between CCS and non-CCS groups (log-rank p = 0.35) or between TCZ and non-TCZ groups (log-rank p = 0.69). ORR, CRR, and OS were also comparable between evaluated groups. In our multivariable model, administering CCS with/without TCZ for CRS/ICANS management did not independently influence PFS (HR, 0.74; 95% CI, 0.36-1.51). These findings suggest that, among patients with relapsed/refractory MM, the timely and appropriate use of CCS or TCZ for mitigating immune-mediated toxicities does not appear to impact the antitumor activity and long-term outcomes of CAR T-cell therapy.
Keyphrases
- multiple myeloma
- cell therapy
- free survival
- rheumatoid arthritis
- acute lymphoblastic leukemia
- acute myeloid leukemia
- stem cells
- diffuse large b cell lymphoma
- mesenchymal stem cells
- hodgkin lymphoma
- single cell
- randomized controlled trial
- bone marrow
- juvenile idiopathic arthritis
- low dose
- case report
- electronic health record
- machine learning
- rheumatoid arthritis patients
- big data
- kidney transplantation
- systemic lupus erythematosus
- deep learning