Efficacy and Safety of CAR-T Therapy for Relapse or Refractory Multiple Myeloma: A systematic review and meta-analysis

Abstract

Background: Multiple myeloma (MM) is incurable in spite of recent treatment improvements, highlighting the development of new therapies. Chimeric antigen receptor (CAR) T-cell therapy has dramatically changed the therapeutic effectiveness in high-risk B-cell malignancies. For relapsed/refractory multiple myeloma (RRMM), preclinical evaluations of CAR-T therapy have shown promising efficacy, thus various active clinical trials are under way. Herein, we conducted this review to summarize efficacy and safety of CAR-T therapy and provide more evidence to guide clinical treatments. Method: We systematically searched literature based on databases (PubMed, EMBASE, Cochrane Central Register of Controlled Trials), and conference abstracts reported from American Society of Hematology (ASH), European Hematology Association (EHA) and American Society of Clinical Oncology (ASCO), in addition to other sources (www.clinicaltrials.gov, article citations). Data assessed efficacy and safety of CAR-T therapy in patients with RRMM were extracted and evaluated, and then systematically analyzed by Comprehensive Meta-analysis 3.0 (CMA 3.0). Results: A total of 23 studies including 350 participants from different countries, diagnosed as RRMM and treated with CAR-T therapy (containing 7 antigens targeted by CARs) were combined. In summary, we discovered the pooled overall response rate (77%), complete response rate (37%) and minimal residual disease (MRD) negativity rate within responders (78%). Furthermore, the pooled relapse rate of responders was 38% and median progression-free survival was 8 months. The pooled survival rate was 87% at last follow-up (median, 12 months). In addition, the pooled grade 3-4 rates of cytokine release syndrome (CRS) and neurologic toxicities (NT) were 14% and 13%, respectively. Conclusion: Our study suggests that CAR-T therapy has demonstrated efficacy and safety in RRMM patients. BCMA-targeted CAR-T and anti-BCMA contained regimen have shown better efficacy.

Management of Renal Failure in Multiple Myeloma

“…• No data are available about dose modifications of promising and effective treatment as CAR-T cells [122][123][124] therapy, bi-specific antibodies [125][126][127], and other agents as Venetoclax [128][129][130], Melfuflen [131][132][133], and Iberdomide [134,135] in case of renal impairment, and particularly dialysis-dependence.…”

Title: Risk factors for non-infectious diarrhea of patients with multiple myeloma after chimeric antigen receptor T-cell immunotherapy: A retrospective observational study

“…Emerging studies support the good effectiveness and safety of CAR-T therapy on the population with relapsed / refractory MM [5][6]. A meta-analysis reported that the survival rate of MM patients within 12 months after CAR-T therapy reached to 78% [7]. Moreover, Guo et al found that among ve patients with relapsed/refractory MM who received CD138z CAR-T therapy, four patients were in stable disease longer than three months, one patient with advanced plasma cell leukemia had a reduction of the myeloma cells in her peripheral blood (from 10.5-3%) [8].…”

Association of extensive RNA disruption with natural killer cell-mediated death of K562 chronic myelogenous leukemia cells

“…For example, < 20% of lung cancer patients and < 45% of patients with malignant melanoma respond to PDL1 inhibitors 36,37 . Similarly, recent reviews indicate that objective and complete response rates to CAR T cell therapy vary widely from study to study [38][39][40] . Given the large number of nonresponding patients, and the costs and toxicities associated with the above immunotherapies, a biomarker that could effectively predict treatment outcome prior to treatment or early during treatment would be highly valued.…”