Systematic Literature Review and Network Meta-Analysis of Treatment Outcomes in Relapsed and/or Refractory Multiple
Chrissy H Y van Beurden-Tan1, Margreet G Franken1, Hedwig M Blommestein1
1Chrissy H.Y. van Beurden-Tan and Pieter Sonneveld, Erasmus MC Cancer Institute; Margreet G. Franken, Hedwig M. Blommestein, and Carin A. Uyl-de Groot, Erasmus University Rotterdam, Rotterdam; and Hedwig M. Blommestein and Carin A. Uyl-de Groot, Comprehensive Cancer Organisation, Utrecht, the Netherlands.
Abstract:
Purpose Since 2000, many new treatment options have become available for relapsed and/or refractory multiple myeloma (R/R MM) after a long period in which dexamethasone and melphalan had been the standard treatment. Direct comparisons of these novel treatments, however, are lacking. This makes it extremely difficult to evaluate the relative added value of each new treatment. Our aim was to synthesize all efficacy evidence, enabling a comparison of all current treatments for R/R MM. Methods We performed a systematic literature review to identify all publicly available phase III randomized controlled trial evidence. We searched Embase, MEDLINE, MEDLINE In-Process, Cochrane Central Register of Controlled Clinical Trials, and the Web site www.ClinicalTrials.gov . In addition, two trials presented at two international hematology congresses (ie, ASCO 2016 and European Hematology Association 2016) were added to include the most recent evidence. In total, 17 randomized controlled trials were identified, including 18 treatment options. The evidence was synthesized using a conventional network meta-analysis. To include all treatments within one network, two treatment options were combined: (1) bortezomib monotherapy and bortezomib plus dexamethasone, and (2) thalidomide monotherapy and thalidomide plus dexamethasone. Results The combination of daratumumab, lenalidomide, and dexamethasone was identified as the best treatment. It was most favorable in terms of (1) hazard ratio for progression-free survival (0.13; 95% credible interval, 0.09 to 0.19), and (2) probability of being best (99% of the simulations). This treatment combination reduced the risk of progression or death by 87% versus dexamethasone, 81% versus bortezomib plus dexamethasone, and 63% versus lenalidomide plus dexamethasone. Conclusion Our network meta-analysis provides a complete overview of the relative efficacy of all available treatments for R/R MM. Until additional data from randomized studies are available, on the basis of this analysis, the combination of daratumumab, lenalidomide, and dexamethasone seems to be the best treatment option.
Insights
The best treatment for relapsed/refractory multiple myeloma (R/R MM) is daratumumab, lenalidomide, and dexamethasone. This combination significantly reduces progression or death risk compared to other options, offering a new standard of care.
Area of Science:
- Hematology
- Oncology
- Clinical Trials Research
Background:
- Multiple myeloma (MM) treatment landscape has evolved significantly since 2000.
- Novel therapies are available for relapsed and/or refractory multiple myeloma (R/R MM).
- Direct comparative data for R/R MM treatments are limited, hindering treatment selection.
Purpose of the Study:
- To synthesize efficacy evidence from phase III randomized controlled trials (RCTs) for R/R MM.
- To enable a comparative evaluation of all current R/R MM treatment options.
- To identify the most effective treatment strategy for R/R MM.
Main Methods:
- Systematic literature review of phase III RCTs for R/R MM.
- Inclusion of data from Embase, MEDLINE, Cochrane, and ClinicalTrials.gov.
- Network meta-analysis to synthesize evidence from 17 RCTs encompassing 18 treatment options.
Main Results:
- The combination of daratumumab, lenalidomide, and dexamethasone demonstrated superior efficacy.
- This regimen showed a hazard ratio of 0.13 for progression-free survival (95% CI: 0.09–0.19).
- It reduced the risk of progression or death by up to 87% compared to single-agent dexamethasone.
Conclusions:
- Network meta-analysis provides a comprehensive efficacy overview for R/R MM treatments.
- Daratumumab, lenalidomide, and dexamethasone combination is identified as the most favorable treatment.
- This combination represents a potential new standard of care for R/R MM pending further randomized data.
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