Efficacy and Safety of Chimeric Antigen Receptor T-Cell Therapy in Relapsed and Refractory Multiple Myeloma - a Meta-Analysis

• Published in: Blood 2024-11, Vol.144, p.2008-2008
• Main Authors: Iftikhar, Ahmad, Shahani, Hiba Arshad, Rehman, Mohammad Ebad Ur, Hameed, Muhammad Sheraz, Abidi, Syed Ali Raza, Ayoobkhan, Fathima Shehnaz, Ahmad, Rana Uzair, Quadri, Afreen, Suhaib, Muhammad, A Safdar, Omar, Anwer, Faiz, Husnain, Muhammad
• Format: Article
• Language: English
• ISSN: 0006-4971
• DOI: 10.1182/blood-2024-209502

Introduction: Multiple myeloma (MM) is the second most common hematological malignancy. The use of Proteosome Inhibitors (PI), Immunomodulatory drugs (IMIDs), anti-CD 38 monoclonal antibodies, and autologous stem cell transplant has improved the survival, but MM remains incurable with inevitable relapse and refractoriness to multiple lines of chemotherapies. Chimeric Antigen Receptor T-cell (CAR T-cell) therapy has shown efficacy in relapsed and refractory multiple myeloma (RRMM) patients. However, the use of CAR T-cell therapy is associated with the risk of several toxicities. Cytokine release syndrome (CRS) is the most common, with cytopenias, neurotoxicity, risk of infections and cardiovascular toxicities are also possible. In this meta-analysis, we aim to evaluate the efficacy and toxicities associated with the use of CAR T- cell therapy in RRMM. Materials and methods: We performed a comprehensive literature search on Pubmed, Cochrane, Embase databases on 07/01/2024 from inception. We used MeSH terms and keywords as “Multiple Myeloma”, “myeloma”, and “Chimeric Antigen Receptor T-cell therapy”. A total of 176 clinical trials were identified. We included phase I/II/III clinical trials using CAR-T cell therapy in RRMM. Two authors independently screened the articles, and any discrepancies were resolved by third author. We included the trials that had documented efficacy outcomes and clearly reported hematological, neurological, cardiovascular toxicities including CRS. Pooled prevalences were calculated using a random effects meta-analysis following Freeman-Tukey Double Arcsine Transformation in MetaXL. Results: After removing duplicates, we included 34 clinical trials (n = 1777 patients) in our metanalysis. All patients had relapsed to at least ≥ 2 prior lines of therapy. We included 7 trials each of Ciltacabtagene autoleucel (cilta-cel) and Idecabtagene vicleucel (ida-cel) while 21 trials used different CAR-T cell therapies including GPRC5D, HDS269B, C-CAR088, HBI0101, CART-ddBCMA, ALLO-715, ARI0002h. The pooled prevalence of overall survival (OS) and progression free survival (PFS) were 72% (95% CI 58-83, I2 90%) and 51% (95% CI 42-59, I2 73%), respectively. Overall response rate (ORR) was 89% (95% CI 85-93, I2 86%). Complete response (CR) and stringent complete response (sCR) were 41% (95% CI 33-49, I2 88%) and 40% (95% CI 32-49, I2 88%), respectively. Partial response was reported in 19% (95% CI 12-29, I2 82%) of patients. In a subgroup analysis, the