The efficacy and safety of CAR-T therapy in relapsed or refractory multiple myeloma patients: a systematic review and meta-analysis

Cost per Responder Analysis to Assess the Value of CAR-T Therapy for Relapsed or Refractory Multiple Myeloma

Optimizing fludarabine: The impact of fludarabine renal dose adjustment during lymphodepletion prior to CAR-T cell immunotherapy in multiple myeloma patients

Effects of Consolidation Therapy With Autologous Hematopoietic Stem Cell Transplantation After BCMA-CAR T-Cell Therapy on the Survival of Patients With Relapsed or Refractory Multiple Myeloma

Chimeric antigen receptor (CAR) T-cell therapy has emerged as a promising treatment for relapsed or refractory multiple myeloma (RRMM), with high response rates of 80–95%. Serum immunoglobulin changes have been observed throughout conventional multiple myeloma treatment, including after immunomodulatory drugs, proteasome inhibitors, and autologous stem cell transplantation. However, the clinical significance of new abnormal protein bands (APBs) following CAR T-cell therapy is largely unexplored. We retrospectively analyzed consecutive multiple myeloma (MM) patients who received CAR T-cell therapy at the University Hospital Bern between May 2021 and February 2024. Serum paraprotein (M-protein) patterns were assessed using immuno-fixation electrophoresis (IFE) before and after CAR T-cell treatment. Patients were grouped based on serum immunoglobulin changes. Among 46 patients, 9 (19.6%) developed new APBs following CAR T-cell therapy. No significant differences in overall survival (OS) or progression-free survival (PFS) were observed between patients with and without APBs. Immunoglobulin changes occurred in both relapsed and non-relapsed patients, suggesting that the appearance of new APBs does not indicate disease progression. This observation aligns with previous reports of paraprotein changes following conventional MM therapies. This report suggests that new APBs following CAR T-cell therapy are a relatively common finding but do not correlate with inferior clinical outcomes. Our results highlight the need for larger, multi-center studies to further investigate this phenomenon in MM patients undergoing CAR T-cell therapy.

A Single-Center, Single-Arm, Phase I Clinical Trial of Anti-BCMA/GPRC5D Bispecific CAR T-Cells in Patients with Refractory and Relapsed Multiple Myeloma with Extramedullary Disease

This meta-analysis systematically evaluated the efficacy and safety of B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T-cell therapy in patients with relapsed or refractory multiple myeloma (RRMM) with extramedullary disease (EMD). PubMed, Embase, Web of Science, and the Cochrane Library were searched for studies published up to December 2024 reporting CAR T-cell therapy in RRMM patients with EMD. Studies were screened according to predefined inclusion and exclusion criteria. Data were extracted and the methodological quality was assessed using the Newcastle-Ottawa Scale (NOS) and the MINORS tool; one low-quality study was excluded. A total of 42 studies were included, comprising 242 RRMM patients with EMD and 1,485 without EMD. Fixed- or random-effects models were applied to pool effect sizes. Primary outcomes included objective response rate (ORR), complete response (CR), progression-free survival (PFS), and overall survival (OS). Secondary outcomes included cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). The pooled ORR and CR rates were 79% (95%CI: 71%-86%) and 42% (95%CI: 32%-51%) in the EMD group, and 90% (95%CI: 86%-93%) and 49% (95%CI: 40%-58%) in the non-EMD group, respectively. Reported median PFS ranged from 3 to 18.8 months in the EMD grouPand from 1 to 38 months in the non-EMD group, while median OS ranged from 6 to 13.9 months and from 12.2 to 38 months, respectively. The pooled incidences of grade ≥3 CRS and ICANS were 18% (95%CI: 8%-27%) and 5% (95%CI: 3%-7%) in the EMD group, compared with 13% (95%CI: 7%-19%) and 6% (95%CI: 2%-9%) in the non-EMD group; none of the differences were statistically significant (P> 0.05). Due to inconsistent reporting and lack of individual patient-level data, hazard ratios and pooled time-to-event analyses were not feasible. Although RRMM patients with EMD exhibited lower ORR and CR rates than those without EMD, BCMA-directed CAR T therapy demonstrated notable clinical activity with a manageable safety profile. However, no direct comparisons with conventional therapies were performed in this analysis. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42025613422, identifier CRD42025613422.

Three-Year Follow-up on Efficacy and Safety Results from Phase 1 Lummicar Study 1 of Zevorcabtagene Autoleucel in Chinese Patients with Relapsed or Refractory Multiple Myeloma

Efficacy of Chimeric Antigen Receptor T-Cell Therapy Is Not Impaired By Previous Bispecific Antibody Treatment in Patients with Large B-Cell Lymphoma

Isotype-specific heavy/light chain quantification identifies prognostic biomarkers after ARI0002h BCMA-directed CAR-T cell therapy in multiple myeloma

Successful Development of an Outpatient Chimeric Antigen Receptor (CAR) T Cell Therapy Program

Anti-GPRC5D CAR T-cell therapy as a salvage treatment in patients with progressive multiple myeloma after anti-BCMA CAR T-cell therapy: a single-centre, single-arm, phase 2 trial.

Promoter usage regulating the surface density of CAR molecules may modulate the kinetics of CAR-T cells in vivo

Background Chimeric antigen receptor (CAR) T-cell therapy shows impressive results in clinical trials. We conducted a meta-analysis based on the most recent data to systematically describe the efficacy and safety of anti-BCMA CAR T therapy for patients with relapsed or refractory multiple myeloma (R/R MM). Methods PubMed, Embase, Web of Science, Cochrane library, ClinicalTrials.gov, China Biology Medicine disc (CBM disc) and Wanfang Data were searched on 8 November 2020. Registration number of PROSPERO was CRD42020219127. Results From 763 articles, we identified 22 appropriate studies with 681 patients. The pooled overall response rate (ORR) was 85.2% (95%CI 0.797–0.910), complete response rate (CRR) was 47.0% (95%CI 0.378–0.583), and minimal residual disease (MRD) negativity rate was 97.8% (95%CI 0.935–1.022). The pooled incidence of grade 3–4 cytokine release syndrome was 6.6% (95%CI 0.036–0.096) and neurotoxicity was 2.2% (95%CI 0.006–0.038). The median progression-free survival (PFS) was 14.0 months and median overall survival (OS) was 24.0 months. Subgroup analysis showed dual epitope-binding CAR T cells achieved the best therapy outcomes and humanized CAR T cells had the best safety profile. Patients who were older, heavily pre-treated or received lower dose of CAR T cells had worse ORR. There was no significant difference in ORR, CRR and PFS between patients with and without high-risk cytogenetic features. The PFS and CRR of non-extramedullary disease (EMD) group was superior to those of EMD group. Conclusion Anti-BCMA CAR T therapy is effective and safe for patients with R/R MM. It can improve the prognosis of patients with high-risk cytogenetic features while the prognosis of patients with EMD remains poor. Moreover, patients are likely to benefit from an earlier use of CAR T therapy and human-derived CAR T cells have obvious advantages based on the existing data.

BMS-986393 (CC-95266), a G Protein-Coupled Receptor Class C Group 5 Member D (GPRC5D)-Targeted Chimeric Antigen Receptor (CAR) T-Cell Therapy for Relapsed/Refractory Multiple Myeloma (RRMM): Updated Results from a Phase 1 Study

BackgroundB-cell maturation antigen (BCMA)-directed chimeric antigen receptor T-cell (CAR-T) therapy exhibits high response rates in patients with relapsed/refractory multiple myeloma (r/r MM). However, the specific factors that influence the response duration remain poorly understood.MethodsThis single-centre, retrospective observational study included 56 patients with r/r MM who received BCMA CAR-T therapy (equecabtagene autoleucel) at Tongji Hospital, China. We analysed response rates and long-term clinical outcomes and identified key factors contributing to the long-term efficacy of BCMA CAR-T therapy.ResultsAt a median follow-up of 39.6 months, the overall response rate (ORR) was 96.4%. Among the patients, 96.4% (54 of 56) achieved minimal residual disease (MRD) negativity, whereas 80.4% (45 of 56) achieved complete response (CR) or stringent complete response (sCR). Poorer outcomes were observed in patients with triple exposure, high cytogenetic risk, or failure to achieve CR. Better outcomes were associated with a CAR-T cell persistence of at least six months and sustained MRD negativity. Prolonged MRD negativity was strongly correlated with longer progression-free survival (PFS), with median PFS durations of 58 months, 64 months, and not reached (NR) for patients who maintained MRD negativity for 12, 24, and 36 months, respectively. Patients who remained MRD-negative and progression-free exhibited higher CAR-T cell expansion peaks. Additionally, CAR-T cell persistence was positively correlated with the duration of MRD negativity duration, PFS, and overall survival (OS).ConclusionsBCMA CAR-T therapy provides durable responses in a subset of patients with r/r MM. Early intervention may improve patient prognosis by promoting sustained MRD negativity, thus improving overall treatment outcomes.Trial registrationTrial registration Chinese Clinical Trial Registry, ChiCTR2000033946 (https://www.chictr.org.cn/showproj.html?proj=53503), Registered June 18, 2020. Trial registration Chinese Clinical Trial Registry, ChiCTR1800018137 (https://www.chictr.org.cn/showproj.html?proj=30653), Registered August 31, 2018.