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SERGIO SIRAGUSA

Network meta-analysis of randomized trials in multiple myeloma efficacy and safety in frontline therapy for patients not eligible for transplant

  • Authors: Botta, Cirino; Gigliotta, Emilia; Paiva, Bruno; Anselmo, Rita; Santoro, Marco; Otero, Paula Rodriguez; Carlisi, Melania; Conticello, Concetta; Romano, Alessandra; Solimando, Antonio Giovanni; Cerchione, Claudio; Da Vià, Matteo; Bolli, Niccolò; Correale, Pierpaolo; Di Raimondo, Francesco; Gentile, Massimo; San Miguel, Jesus; Siragusa, Sergio
  • Publication year: 2022
  • Type: Articolo in rivista
  • OA Link: http://hdl.handle.net/10447/563860

Abstract

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. This article is protected by copyright. All rights reserved.