Smith Giri, MD, MHS Institute for Cancer Outcomes and Survivorship, Division of Hematology and Oncology The University of Alabama at Birmingham speaks about the Evaluation of Daratumumab for the Treatment of Multiple Myeloma in Patients With High-risk Cytogenetic Factors.
Core Points
Question Is there a gain in patients with cytogenetically identified high-risk multiple myeloma (HRMM) associated with the addition of daratumumab to backbone myeloma treatment regimens?
Findings Six clinical studies affecting 4061 patients were found during this systematic examination and meta-analysis, of which 580 had HRMM. In patients with newly diagnosed HRMM or relapsed or refractory HRMM, the addition of daratumumab to the backbone multiple myeloma regimens was associated with substantially improved progression-free survival.
Significance The results indicate that the addition of daratumumab to the existing myeloma regimens may be correlated with improved outcomes for HRMM patients.
Instract
Importance Increased response rates and progression-free survival are associated with the addition of daratumumab to backbone multiple myeloma (MM) regimens (PFS). It remains uncertain whether enhanced outcomes among patients with cytogenetically specified high-risk MM (HRMM) are also correlated with this regimen.
Objective To assess PFS in patients with HRMM consistent with the addition of daratumumab to backbone MM regimens.
Data Sources From the beginning of January 2, 2020, MEDLINE, Embase, PubMed, Scopus, Web of Science Core Collection, Cochrane Library, clinical trials registries, and meeting libraries were searched using words representing multiple myeloma and daratumumab for this systematic review and meta-analysis.
SELECTION OF THE Research Phase 3 randomized clinical trials were included, comparing backbone MM regimens with the same protocol plus daratumumab in newly diagnosed or relapsed or refractory MM, in such a way that the use of daratumumab was the only distinction between the intervention and control groups and reported cytogenetic risk outcomes. The existence of t(4;14), t(14;16), or del del, was identified as high-risk MM (17p).
Extraction and synthesis of data Using the reporting guideline for Desired Reporting Items for Systematic Reviews and Meta-analyses (PRISMA), 2 researchers independently extracted study data, with a third investigator resolving disagreements. The Cochrane risk-of-bias technique assessed consistency.
Main Outcomes and Tests Hazard ratios (HRs) for PFS were used to collect data on efficacy. Using a DerSimonian-Laird random-effects model, relative log-HRs were pooled. Using the Cochran Q and I2 figures, heterogeneity was assessed.
RESULTS Of the 5194 studies reviewed, 6 phase 3 studies were eligible, including 3 newly diagnosed MM studies (2528 patients; 358 with HRMM) and 3 relapsed or refractory MMM studies (1533 patients; 222 with HRMM). The addition of daratumumab to backbone regimens in newly diagnosed HRMM patients was correlated with improved PFS (pooled HR, 0.67; 95 percent CI, 0.47-0.95; P = .02), with little evidence of heterogeneity (Cochran Q, P = .77; I2 = 0 percent). Similar findings have been found for patients with relapsed or refractory HRMM (pooled HR, 0.45; 95% CI, 0.30-0.67; P < .001), again with little evidence of heterogeneity (Cochran Q, P = .63; I2 = 0%).
Conclusions and significance This study indicates that improved PFS among patients with newly diagnosed HRMM or relapsed or refractory HRMM may be correlated with the use of daratumumab in backbone regimens.