Network meta-analysis of randomized trials in multiple myeloma efficacy and safety in frontline therapy for patients not eligible for transplant
Cirino Botta 1 , Emilia Gigliotta 1 , Bruno Paiva 2 , Rita Anselmo 1 , Marco Santoro 1 , Paula Rodriguez Otero 2 , Melania Carlisi 1 , Concetta Conticello 3 , Alessandra Romano 3 , Antonio Giovanni Solimando 4 , Claudio Cerchione 5 , Matteo Da Vià 6 7 , Niccolò Bolli 6 7 , Pierpaolo Correale 8 , Francesco Di Raimondo 3 , Massimo Gentile 9 , Jesus San Miguel 2 , Sergio Siragusa 1
The treatment scenario for newly-diagnosed transplant-ineligible multiple myeloma patients (NEMM) is quickly evolving. Currently, combinations of proteasome inhibitors (PI) and/or immunomodulatory drugs (IMiD) +/- 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 (NMA) of 27 phase 2/3 randomized trials including a total of 12935 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 3 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.