Pomalidomide-based regimens for treatment of relapsed and relapsed/refractory multiple myeloma: systematic review and meta-analysis of phase 2 and 3 clinical …

A Mushtaq, A Iftikhar, H Hassan, M Lakhani… - … Myeloma and Leukemia, 2019 - Elsevier
Clinical Lymphoma Myeloma and Leukemia, 2019Elsevier
Abstract Introduction Pomalidomide (Pom) has demonstrated synergistic antiproliferative
activity in combination regimens as a result of its distinct anticancer, antiangiogenic, and
immunomodulatory effects. This review aimed to compare outcome measures of different
Pom regimens for relapsed/refractory multiple myeloma. Methods A comprehensive
literature search identified a total of 1374 studies. Thirty-five studies assessing 4623
subjects met the inclusion criteria: phase 2/3 trial,≥ 2 prior lines of therapy, and clearly …
Introduction
Pomalidomide (Pom) has demonstrated synergistic antiproliferative activity in combination regimens as a result of its distinct anticancer, antiangiogenic, and immunomodulatory effects. This review aimed to compare outcome measures of different Pom regimens for relapsed/refractory multiple myeloma.
Methods
A comprehensive literature search identified a total of 1374 studies. Thirty-five studies assessing 4623 subjects met the inclusion criteria: phase 2/3 trial, ≥ 2 prior lines of therapy, and clearly documented efficacy outcomes like overall response rate (ORR), overall survival, and progression-free survival. Statistical analyses for meta-analysis was performed by CMA version 3 and Cochrane Q statistics (P < .05 considered significant, I2 index for heterogeneity). A random effects model was used if there was significant heterogeneity (P ≥ .05 over I2 ≥ 50%).
Results
Pooled analysis showed ORR 47.1% across all Pom-based (2- and 3-drug) regimens. Stratified analysis for efficacy outcomes (pooled ORR [%] and mean progression-free survival [months]) are reported. With doublet regimen, Pom with low-dose dexamethasone (LoDex) was the most common regimen (35.7%, 6.1 months), and overall survival was 14.37 months. With triplet regimens, pooled ORR was 61.9% (I2 = 87.3%). These included bortezomib + Pom + LoDex (83.5%, 15.7 months), carfilzomib-Pom + LoDex (77.1%, 15.3 months), Pom + LoDex-bendamustine (74.2%), Pom-dexamethasone-daratumumab (64.5%), Pom + LoDex-cyclophosphamide (59.4%, 9.5 months), and Pom + LoDex-doxorubicin (32%). Leading adverse events were myelosuppression, with mean incidences of grade 3 or higher neutropenia, anemia, and thrombocytopenia of 47.6%, 26.5%, and 20.8%, respectively. Mean incidence of grade 3 or higher nonhematologic adverse events were infections 29.1%, pneumonia 13.8%, and fatigue 10%.
Conclusion
Three-drug Pom regimens yielded double the response rates compared to Pom + LoDex (pooled ORR, 61.9% vs. 35.7%), with bortezomib + Pom + LoDex and carfilzomib-Pom + LoDex demonstrating better outcomes than other regimens.
Elsevier
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