T-cell-redirecting therapies in early relapsed multiple myeloma: a systematic review and network meta-analysis.
Maximilian Merz, Joao Tadeu Souto Filho, Peter M Voorhees et al.
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In 30 seconds
This systematic review and network meta-analysis compared T-cell-redirecting regimens in randomized phase 3 trials involving patients with multiple myeloma after at least one prior line. Four trials included 2,174 patients and evaluated ciltacabtagene autoleucel, teclistamab-daratumumab, and talquetamab-daratumumab regimens. Teclistamab-daratumumab ranked highest for progression-free survival under a fixed-effect model, but the apparent advantage was not robust to between-trial heterogeneity: all comparisons crossed unity in the random-effects analysis. Overall survival comparisons were also inconclusive, and the review did not establish an efficacy hierarchy or demonstrate equivalence.
Key findings
- Control-arm median progression-free survival ranged from 9.9 to 24.4 months, with substantial between-trial heterogeneity (I-squared 91%).
- Under fixed effects, teclistamab-daratumumab versus talquetamab-daratumumab had a progression-free survival hazard ratio of 0.55 (95% credible interval 0.34 to 0.88).
- With between-trial heterogeneity included, every progression-free survival contrast crossed unity; versus ciltacabtagene autoleucel, the hazard ratio was 0.62 (0.21 to 1.81).
- Overall survival for teclistamab-daratumumab versus ciltacabtagene autoleucel was 0.94 (0.55 to 1.62); restricted mean survival gains over control were 0.7 to 1.6 months at 24 months.
Why it matters
These therapies are being used earlier in the course of multiple myeloma, but indirect comparisons do not provide a dependable basis for ranking them by efficacy. The marked variation in control-arm outcomes and sensitivity of progression-free survival comparisons to modelling assumptions underscore the uncertainty. Toxicity, treatment sequencing, access, and cost may therefore be relevant alongside efficacy when considering these regimens.
What to keep in mind
The comparisons were indirect and based on four trials with substantial variation in control-arm progression-free survival. Toxicity burden could not be reliably compared across trials, and the analysis did not establish equivalence.