Daratumumab-based three drug regimens for high-risk multiple myeloma: A meta-analysis.

Abstract

e20549 Background: Efficacy of daratumumab (D) based regimens in high risk multiple myeloma (MM) (i.e, ISS stage II/III and t(4;14) or (del17p)) has not been thoroughly investigated. The aim of this study was to assess the efficacy of D based 3-drug regimens compared to non-D based regimens in high risk MM. Methods: A systematic review of literature was performed to identify randomized controlled trials (RCTs) which reported overall response rates (ORR) and progression free survival (PFS) of MM patients (pts) with D based 3-drug regimens. Odds ratios (OR) of ORR were computed and hazard ratios (HR) of PFS (along with 95% confidence intervals; CI) were extracted to compute a pooled HR using RevMan v.5.3 to report the efficacy of D based 3-drug regimens. A random effects model was employed only when there was significant heterogeneity among studies ( > 40%, as assessed by I-squared). Results: Screening of 604 studies yielded 04 RCTs (n = 2,234 pts). D was evaluated with lenalidomide (L), carfilzomib (C), bortezomib (B) and dexamethasone (d). DLd regimen was studied in 649, DCd in 312 and DBd in 240 pts. Total 1201 pts were evaluated with D. D based 3-drug regimens proved to be of improved efficacy versus non-D 2-drug regimens in the pooled analysis i.e., PFS (HR 0.46, 95% CI 0.33-0.63; p < 0.00001; I2 = 81%) and ORR (OR 2.83, 95% CI 2.06-3.88; p < 0.00001; I2 = 44%). Relapsed/refractory MM (n = 833) also showed improved ORR (OR 2.79, 95% CI 1.78-4.36; p < 0.00001; I2 = 62%). In high risk group, addition of D decreased the risk of progression to 42% (HR 0.58, 95% CI 0.39-0.85; p = 0.005; I2 = 3%). In standard risk pts, D decreased the risk of progression/death to 66% (HR 0.34, 95% CI 0.23-0.51; p < 0.00001; I2 = 74%). D increased the risk of neutropenia (OR 1.88, 95% CI 1.54-2.31; p < 0.00001; I2 = 0%), respiratory tract infections (OR 1.87, 95% CI 1.49-2.35; p < 0.00001; I2 = 0%) and diarrhea (OR 1.83, 95% CI 1.46-2.29; p < 0.00001; I2 = 23%) in the study population. Conclusions: Daratumumab based 3-drug regimens appear to abrogate high risk features in MM compared to 2 drug regimens.