Pomalidomide Based Regimens for Treatment of Relapsed and Relapsed/Refractory Multiple Myeloma: A Systematic Review and Meta-analysis of Phase II and Phase III Clinical Trials

Abstract Introduction Pomalidomide (Pom) has demonstrated synergistic anti-proliferative activity in combination regimens due to its distinct anti-cancer, anti-angiogenic and immunomodulatory effects. This study aims to compare outcome measures of different Pom-regimens for relapsed refractory multiple myeloma. Methods Comprehensive literature search identified a total of 1374 studies. 35 studies (n=4623) met the inclusion criteria; phase II/III trial, ≥ 2 prior lines of therapy and clearly documented efficacy outcomes like overall response rate(ORR), overall survival(OS), progression free survival(PFS). Statistical analyses for meta-analysis was performed using CMA version 3 and Cochrane Q statistics ( p I 2 index for heterogeneity). A random effect model was used if there was significant heterogeneity p ≥0.05 over I 2 ≥50%. Results Pooled analysis showed ORR 47.1% across all Pom based (two and three drug) regimens. Stratified analysis for efficacy outcomes [Pooled ORR (%), Mean PFS (Months/Mo)] are reported. With doublet regimen, Pom–LoDex was the most common regimen (35.7%, 6.1 Mo) and OS=14.37. With triplet regimens, pooled ORR was 61.9%, I 2 = 87.3%. These included: Bort-Pom-LoDex (83.5%, 15.7 Mo), CFZ-Pom-LoDex (77.1%, 15.3 Mo), Pom-LoDex-Bendamustine (74.2%), Pom-Dex-daratumumab (64.5%), Pom-LoDex-cyclophosphamide (59.4%, 9.5 Mo), Pom-LoDex-doxorubicin (32%). Leading adverse events (AE) were myelosuppression with mean incidences of grade ≥3 neutropenia, anemia and thrombocytopenia being 47.6%, 26.5% and 20.8% respectively. Mean incidence of grade ≥3 non-hematological AE were infections 29.1%, pneumonia 13.8% and fatigue 10%. Conclusion Three drug Pom-regimens yielded double the response rates when compared with Pom-LoDex (pooled ORR 61.9% vs 35.7%), with Bort-Pom-LoDex and CFZ-Pom-LoDex demonstrating better outcomes than others.