Effect modification in network meta-analyses for relapsed/refractory multiple myeloma: systematic review and...

Area of Science:

• Hematology
• Clinical Trials
• Biostatistics

Background:

• Relapsed/refractory multiple myeloma (RRMM) presents treatment challenges.
• Network meta-analyses (NMAs) are crucial for comparing treatments but assume minimal effect modification.
• Understanding effect modification is key to validating NMA results.

Purpose of the Study:

• To systematically review and meta-analyze evidence on effect modification by refractory status and treatment lines in RRMM.
• To assess if effect modification invalidates NMAs that assume negligible modification.

Main Methods:

• Systematic literature search and meta-analysis of randomized controlled trials (Phase 2/3).
• Estimation of relative hazard ratios (RHRs) for overall survival (OS) and progression-free survival (PFS).
• Simulation to quantify the impact of effect modification on NMA results.

Main Results:

• Weak evidence for effect modification across 42 publications and 8364 patients.
• Largest RHR for refractory status on PFS was 1.32 (95% CI 1.18-1.49).
• Simulations indicated <5% NMA estimates would differ significantly due to effect modification.

Conclusions:

• Effect modification in RRMM is generally small and can be neglected in NMAs.
• NMAs for OS and PFS in RRMM are likely reliable.
• Results support the validity of NMAs for treatment comparisons in RRMM.