No Clear Efficacy Ranking for T-Cell–Redirecting Therapies in Early Relapsed Myeloma

Available randomized evidence does not establish an efficacy hierarchy among the T-cell-redirecting regimens studied in early relapsed multiple myeloma, according to a systematic review and network meta-analysis in Journal of Hematology & Oncology.

Indirect comparisons in heavily pretreated patients have favored chimeric antigen receptor T-cell therapy, but whether that holds in early relapse was unknown, the authors noted. They analyzed 4 randomized phase 3 trials (2,174 patients): CARTITUDE-4 (ciltacabtagene autoleucel [cilta-cel]), MajesTEC-3 (teclistamab-daratumumab), MonumenTAL-3 (talquetamab-daratumumab with or without pomalidomide), and APOLLO, which anchored a shared daratumumab-pomalidomide-dexamethasone-type control. Pseudo-individual patient survival data were reconstructed from published curves.

Control-arm median progression-free survival (PFS) ranged from 9.9 to 24.4 months across trials (I², 91%). Under a fixed-effect model, teclistamab-daratumumab ranked first for PFS, and only 1 of 6 pairwise contrasts was significant: teclistamab-daratumumab vs talquetamab-daratumumab (hazard ratio [HR], 0.55; 95% credible interval [CrI], 0.34-0.88). With between-trial heterogeneity incorporated in a random-effects model, no contrast was significant, including teclistamab-daratumumab vs cilta-cel (HR, 0.62; 95% CrI, 0.21-1.81). In an intention-to-treat analysis that included control patients receiving other regimens, 3 of 6 fixed-effect contrasts were significant, but none were significant under random effects. Overall survival did not differ significantly under either model (teclistamab-daratumumab vs cilta-cel HR, 0.94; 95% CrI, 0.55-1.62), and equivalence could not be demonstrated.

Safety, assessed descriptively, could not be reliably compared across trials, the authors said. Cytokine release syndrome occurred in 75% of cilta-cel recipients, 60% with teclistamab-daratumumab, and 58% to 68% with the talquetamab regimens. Cilta-cel was associated with delayed neurotoxicity, including parkinsonism in about 1%, whereas talquetamab regimens carried predominantly low-grade dysgeusia, skin and nail toxicity, ataxia, and weight loss. In a US drug-acquisition cost analysis, cost per progression-free month was lowest for cilta-cel, although the authors said the use of list prices without present-value adjustment likely overstates that advantage.

The authors noted that the analysis relied on indirect comparisons of open-label trials with differing populations and described the findings as hypothesis-generating. Until comparative data exist, they concluded, treatment selection will be informed by patient- and disease-related factors, toxicity, sequencing, access, and cost.

Source: Merz M, Souto Filho JT, Voorhees PM, et al. T-cell-redirecting therapies in early relapsed multiple myeloma: a systematic review and network meta-analysis. J Hematol Oncol. 2026;19(1):83. doi:10.1186/s13045-026-01850-2