Efficacy and safety of ixazomib-lenalidomide-dexamethasone in relapsed/refractory multiple myeloma patients

To evaluate the therapeutic efficacy and safety profile of the ixazomib-lenalidomide-dexamethasone (IRd) combination in patients with relapsed/refractory multiple myeloma (RRMM).

Between May 2022 and January 2025, 120 RRMM patients were assigned to a control group (n=52) receiving lenalidomide-dexamethasone (Rd) or an observation group (n=68) treated with IRd. Comparative analyses were conducted to assess therapeutic effectiveness, safety (fatigue, infections, gastrointestinal disturbances, peripheral neuropathy, thrombocytopenia, and leukopenia), bone turnover markers (alkaline phosphatase [ALP], osteocalcin [BGP], C-terminal telopeptide of type I collagen [CTX-I]), inflammatory markers (C-reactive protein [CRP], interleukin-6 [IL-6], tumor necrosis factor-alpha [TNF-α]), and other serum biomarkers (erythrocyte sedimentation rate [ESR], M protein, β₂-microglobulin [β₂-MG]). Predictive factors for treatment response were identified through univariate and multivariate regression modeling.

The observation group demonstrated superior overall effectiveness compared to the control group (P<0.05), without significant differences in adverse event incidence (P>0.05). Post-treatment evaluations showed significantly greater reductions in CTX-I, CRP, IL-6, TNF-α, ESR, M-protein, and β₂-MG levels in the IRd cohort, alongside increased ALP and BGP levels (all P<0.05). Univariate analysis identified Revised International Staging System (R-ISS) classification, IL-6, ESR, M-protein levels, and treatment protocol as significant predictors of therapeutic response (all P<0.05). Multivariate modeling confirmed M-protein concentration as an independent prognostic factor (P<0.05).

The IRd regimen demonstrates enhanced clinical efficacy in RRMM management, maintaining a safety profile comparable to the conventional Rd regimen. Furthermore, it effectively improves bone metabolism, reduces serum inflammation, and modulates serum biochemical parameters. Elevated M-protein expression correlates with poorer treatment outcome in RRMM.