Haematologica (Feb 2020)

Carfilzomib, cyclophosphamide and dexamethasone for newly diagnosed, high-risk myeloma patients not eligible for transplant: a pooled analysis of two studies

  • Roberto Mina,
  • Francesca Bonello,
  • Maria Teresa Petrucci,
  • Anna Marina Liberati,
  • Concetta Conticello,
  • Stelvio Ballanti,
  • Pellegrino Musto,
  • Attilio Olivieri,
  • Giulia Benevolo,
  • Andrea Capra,
  • Milena Gilestro,
  • Piero Galieni,
  • Michele Cavo,
  • Agostina Siniscalchi,
  • Antonio Palumbo,
  • Vittorio Montefusco,
  • Gianluca Gaidano,
  • Paola Omedé,
  • Mario Boccadoro,
  • Sara Bringhen

DOI
https://doi.org/10.3324/haematol.2019.243428
Journal volume & issue
Vol. 106, no. 4

Abstract

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Despite remarkable advances in the treatment of multiple myeloma in the last decades, the prognosis of patients harboring high-risk cytogenetic abnormalities remains dismal as compared to that of standard-risk patients. Proteasome inhibitors demonstrated to partially ameliorate the prognosis of high-risk patients. We pooled together data from two phase I/II trials on transplant-ineligible patients with multiple myeloma receiving upfront carfilzomib cyclophosphamide and dexamethasone followed by carfilzomib maintenance. The aim of this analysis was to compare treatment outcomes in patients with standard- versus high-risk cytogenetic abnormalities detected by fluorescence in situ hybridization (FISH) analysis. High risk was defined by the presence of at least one chromosomal abnormality, including t(4;14), del17p and t(14;16). Overall, 94 patients were included in the analysis: 57 (61%) in the standard-risk and 37 (39%) in the high-risk group. Median follow-up was 38 months. In standard- vs. high-risk patients, we observed similar progression-free survival (3-year PFS: 52% vs. 43%, respectively; p=0.50), overall survival (3-year OS: 78% vs. 73%; p=0.38), and overall response rate (88% vs 95%; p=0.47), with no statistical differences between the two groups. No difference in terms of progression-free survival was observed between patients with or without del17p. Carfilzomib, used both as induction and maintenance agent for transplant-ineligible newly diagnosed multiple myeloma patients, mitigated the poor prognosis carried by high-risk cytogenetics and resulted into similar progression-free survival and overall survival, as compared to standard-risk patients. ClinicalTrials.gov IDs: NCT01857115 (IST-CAR-561) and NCT01346787 (IST-CAR-506).