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Updated: Sep 5, 2025
An Organotypic High Throughput System for Characterization of Drug Sensitivity of Primary Multiple Myeloma Cells
Published on: July 15, 2015
Network meta-analysis of randomized trials in multiple myeloma: Efficacy and safety in frontline therapy for patients
Cirino Botta1, Emilia Gigliotta1, Bruno Paiva2
1Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy.
Abstract:
The treatment scenario for newly-diagnosed transplant-ineligible multiple myeloma patients (NEMM) is quickly evolving. Currently, combinations of proteasome inhibitors and/or immunomodulatory drugs +/- the monoclonal antibody Daratumumab are used for first-line treatment, even if head-to-head comparisons are lacking. To compare efficacy and safety of these regimens, we performed a network meta-analysis of 27 phase 2/3 randomized trials including a total of 12,935 patients and 23 different schedules. Four efficacy/outcome and one safety indicators were extracted and integrated to obtain (for each treatment) the surface under the cumulative ranking-curve (SUCRA), a metric used to build a ranking chart. With a mean SUCRA of 83.8 and 80.08 respectively, VMP + Daratumumab (DrVMP) and Rd + Daratumumab (DrRd) reached the top of the chart. However, SUCRA is designed to work for single outcomes. To overcome this limitation, we undertook a dimensionality reduction approach through a principal component analysis, that unbiasedly grouped the 23 regimens into three different subgroups. On the bases of our results, we demonstrated that first line treatment for NEMM should be based on DrRd (most active, but continuous treatment), DrVMP (quite "fixed-time" treatment), or, alternatively, VRD and that, surprisingly, melphalan as well as Rd doublets still deserve a role in this setting.
Insights
Newly-diagnosed transplant-ineligible multiple myeloma (NEMM) patients benefit from novel treatment combinations. Daratumumab-containing regimens like DrVMP and DrRd show superior efficacy, alongside established options, guiding first-line NEMM therapy selection.
Area of Science:
- Hematology
- Oncology
- Clinical Trials
Background:
- The treatment landscape for newly-diagnosed transplant-ineligible multiple myeloma (NEMM) is rapidly evolving.
- Current first-line NEMM therapies involve proteasome inhibitors and/or immunomodulatory drugs, often with Daratumumab, but direct comparisons are limited.
Purpose of the Study:
- To conduct a network meta-analysis comparing the efficacy and safety of various first-line treatment regimens for NEMM.
- To rank different treatment schedules based on integrated efficacy and safety indicators.
Main Methods:
- Network meta-analysis of 27 phase 2/3 randomized trials with 12,935 NEMM patients.
- Extracted four efficacy/outcome and one safety indicators.
- Utilized Surface Under the Cumulative Ranking Curve (SUCRA) and Principal Component Analysis (PCA) for regimen comparison and grouping.
Main Results:
- Daratumumab plus Velcade, melphalan, and prednisone (DrVMP) and Daratumumab plus lenalidomide (DrRd) ranked highest in overall efficacy (SUCRA 83.8 and 80.08).
- PCA grouped the 23 regimens into three distinct subgroups.
- DrRd, DrVMP, and VRD emerged as preferred first-line options, with melphalan and Rd doublets retaining a role.
Conclusions:
- First-line treatment for NEMM should prioritize DrRd, DrVMP, or VRD based on efficacy and treatment duration.
- The study provides evidence-based guidance for selecting optimal initial therapies in this patient population.
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