Teclistamab Shows Sustained Efficacy in R/R Multiple Myeloma

Across 8 studies reporting overall survival outcomes, teclistamab demonstrated superior outcomes vs SOC, with similar trends observed in 6 studies reporting progression-free survival (PFS) outcomes, in 4 studies reporting time to next treatment, and in 3 studies reporting duration of response.

Teclistamab-cqyv (Tecvayli) as a single agent and in combination therapies showed sustained efficacy vs standard-of-care (SOC) treatments for relapsed/refractory multiple myeloma, according to results from a systemic review and meta-analysis (CRD42025633838) published in Frontiers in Immunology.

Across 34 studies evaluating teclistamab in relapsed/refractory multiple myeloma, 4064 patients were included for analysis. Across 8 studies reporting overall survival (OS) outcomes, teclistamab demonstrated superior outcomes vs SOC (HR, 0.69; 95% CI, 0.54-0.89; P = .037). A similar trend was observed in 6 studies reporting progression-free survival (PFS) outcomes (HR, 0.49; 95% CI, 0.42-0.57; P <.0001), in 4 studies reporting time to next treatment (TTNT; HR, 0.38; 95% CI, 0.30-0.48; P <.0001), and in 3 studies reporting duration of response (DOR; HR, 0.19; 95% CI, 0.06-0.59; P = .0044).

Of 4 studies that reported odds ratios, the overall response rate (ORR) was not significantly different between teclistamab and SOC groups (effect size [ES], 1.69; 95% CI, 0.51-5.58). Additionally, of 3 studies that included relative risks (RRs), the ORR was not significantly different between respective groups (ES, 1.51; 95% CI, 0.64-3.53). However, when excluding data that did not balance baseline characteristics, teclistamab achieved higher response rates compared with SOC treatment options.

Teclistamab also demonstrated superior very good partial response (VGPR) or higher outcomes, with an ES for RR of 5.94 (95% CI, 4.39-8.03) and an ES for OR of 6.55 (95% CI, 1.87-22.96).

Across 11 real-world studies, the pooled ORR among those treated with teclistamab was 62% (95% CI, 58%-66%), with 43% (95% CI, 36%-50%) of patients achieving at least a VGPR, and 22% (95% CI, 16%-28%) achieving at least a complete response (CR).

Additionally, subgroup analyses of single-arm studies evaluating teclistamab as monotherapy and in combination therapies found that the ORR was higher with combination therapies vs single-agent teclistamab: 85% vs 62% (P <.0001). The VGPR or better rates were 68% vs 48% in respective groups (P = .0247), and the CR or better rates were 29% vs 28% (P = .8481). Additionally, the only significant differences in efficacy outcomes between clinical trials and real-world studies were VGPR or better rates (P = .0247) and CR or better rates (P = .0052).

“Teclistamab has demonstrated favorable efficacy in real-world studies and clinical trials and remains a viable and effective treatment option for patients with [relapsed/refractory multiple myeloma] previously exposed to BCMA-targeted therapy,” lead investigator Wenze Li, of the Department of Hematology in The First Affiliated Hospital of China Medical University in Shenyang, China, wrote in the publication with study coinvestigators. “Our research indirectly supports the potential of teclistamab in clinical applications. However, there is still a lack of direct head-to-head studies to demonstrate the efficacy, therefore, we call for more direct comparative clinical trials or real-world studies in the future to validate this conclusion.”

Studies were identified by searching databases including PubMed/MEDLINE, Web of Science, EMBASE, and Cochrane Library. Only the most recent records were included to avoid duplicate data, and studies were derived from conference abstracts. Initially, 2674 studies pertaining to teclistamab in relapsed/refractory multiple myeloma were found. Twelve additional records were identified through hand-searching conference abstracts. After removing 721 duplicate records and reviewing titles and abstracts, 91 articles were identified as potentially relevant.

Following the application of eligibility criteria to full-text review, 34 studies were included in the meta-analysis. Of the included studies, 9 compared teclistamab with existing treatments for relapsed/refractory multiple myeloma, 11 were single-arm trials, and 14 studies assessed the real-world application of teclistamab monotherapy.

Potential trials were selected based on the following criteria: inclusion of patients with relapsed/refractory multiple myeloma; randomized controlled trials or cohort studies; teclistamab monotherapy or combined therapy assessed with no drug dosage restrictions; and clinical outcomes including at least 1 of the following: OS, PFS, TTNT, DOR, ORR, CR or better, VGPR or better, VGPR, PR, or adverse effects (AEs).

In the safety analysis for clinical trials, no significant differences were observed between teclistamab and SOC treatment for immune effector cell-associated neurotoxicity syndrome (ICANS), with an ES of 0.81 (95% CI, 0.53-1.25). Compared to CAR T-cell therapy, teclistamab was significantly associated with lower any-grade cytokine release syndrome (CRS) occurrence, with an ES of 0.77 (95% CI, 0.64-0.93). Furthermore, the pooled analysis rate for any-grade CRS in real-world studies among those who received teclistamab was 57% (95% CI, 53%-61%), and for any-grade ICANS, it was 9% (95% CI, 7%-13%).

Reference

Li W, Zhao D, Jiao Y, Dong W, Wang Z, Yan X. Effectiveness and safety of teclistamab for relapsed or refractory multiple myeloma: a systematic review and meta-analysis. Front Immunol. Published online April 25, 2025. doi:10.3389/fimmu.2025.1565407