Efficacy and Safety of Teclistamab in Relapsed or Refractory Multiple Myeloma: A Systematic Review and Meta-Analysis

Introduction: Multiple myeloma (MM) is a clonal abnormal proliferation of plasma cells resulting in elevated plasma immunoglobulin with end-organ damage with anemia, osteolytic bone lesions, renal failure, and/or hypercalcemia. The FDA approved bispecific antibody Teclistamab, which engages T cells via CD3 ligand and myeloma cells via BCMA binding domain, in October 2022. It has shown promise due to its efficacy and manageable safety profile. This meta-analysis aims to synthesize data on the effectiveness and safety of Teclistamab in treating relapsed or refractory multiple myeloma (RRMM). Methods: The review adhered to PRISMA guidelines, utilizing databases such as PubMed, Web of Science, EMBASE, and Google Scholar to find studies evaluating teclistamab's efficacy and safety. Eligibility criteria included studies involving adult RRMM patients treated with teclistamab, focusing on outcomes like overall response rate (ORR), adverse events, complete response (CR), and excellent partial response (VGPR). On the other hand, safety analysis involved pooling all adverse events of grade 3 or above (grade ≥3 adverse events), including grade ≥3 cytokine release syndrome (CRS) and neurotoxic events. Furthermore, subgroup analyses were conducted to identify factors associated with ORR. Two reviewers independently performed data extraction, and the quality of the included studies was assessed using the Newcastle Ottawa Scale. Results: Five studies with 661 RRMM patients were included in the analysis. The pooled results showed that teclistamab led to an ORR of 62.8% (95% Confidence Interval (CI): 58.6 - 66.8), a ≥VGPR of 52.1% (95% CI: 46.8 - 57.3), and a ≥CR of 29.5% (95% CI: 21.9 - 38.4). When the ORR was assessed in different subgroups, we found that patients with extramedullary disease (EMD) had considerably lower ORR than those without EMD (45% vs. 71%, p<0.0001). Additionally, the ORR was significantly lower in patients with prior BCMA-directed therapy (OR: 2.24, p = 0.002) and those with stage III disease (OR: 3.69, p = 0.0001). However, the subgroup analyses showed no considerable difference in the ORR between patients with high or standard-risk cytogenetics (OR: 1.05 p = 0.82) and those with penta-drug or triple-class-refractory disease (OR: 0.97 p = 0.89). Regarding the safety of teclistamab, the pooled results showed that the incidence of grade ≥3 adverse events was high (90.7%). However, grade ≥3 CRS and neurotoxic events were low (1.5% and 2.2%, respectively). Discussion/Conclusion: RRMM patients treated with teclistamab display good response rates. However, this good response was based on studies with short follow-up duration. Therefore, more research in long-term follow-up studies is required to establish the durability of these responses. In addition, the subgroup analyses suggested that before BCMA-directed therapy, the presence of EMD and stage III disease were associated with poor response rates. However, the response rates for patients with prior BCMA-related therapy are relatively high, meaning teclistamab can also be a valuable therapeutic option for these patients. Teclistamab also displayed low incidences of CRS and neurotoxicity. Therefore, with appropriate measures, resources, and infrastructure, it can be safely administered to patients with RRMM.

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