A real-world efficacy and safety analysis of combined carfilzomib, lenalidomide, and dexamethasone (KRd) in relapsed/refractory multiple myeloma

Hematol Oncol. 2021 Feb;39(1):41-50. doi: 10.1002/hon.2820. Epub 2020 Nov 1.

Abstract

Carfilzomib-lenalidomide-dexamethasone (KRd) has been approved for the treatment of relapsed/refractory multiple myeloma (RRMM). We conducted a retrospective analysis of 197 RRMM patients (pts) between January 2016 and March 2018 in six Italian hematologic centers, with the aim to evaluate efficacy and safety of KRd in real-life. At KRd initiation 27% carried high risk cytogenetic abnormalities (HRCA) [del17p and/or t(4;14) and/or t(14;16)], median number of prior lines of therapy was 2 (1-8), nearly all pts (96%) received prior bortezomib (18% refractory) while 45% were exposed to lenalidomide (R; 22% refractory). At the median of 12.5 months, 52% of the pts had discontinued treatment, mainly (66%) for progression. Main grade 3-4 adverse events were neutropenia (21%), infections (11%), and hypertension (6%). Overall, the response rate was 88%. The median progression-free survival (PFS) was 19.8 months and 1-year overall survival (OS) rate was 80.6%. By subgroup analysis, extended PFS and OS were observed for pts who received ≤2 prior lines of therapy (HR = 0.42, p < 0.001 and HR = 0.35, p = 0.001, respectively), not refractory to prior R (HR = 0.37, p < 0.001, and HR = 0.47, p = 0.024), without HRCA (HR = 0.33, p = 0.005 and HR = 0.26, p = 0.016) and achieving ≥ very good partial response (VGPR; HR = 0.17, p < 0.001 and HR = 0.18, p < 0.001). In conclusion, KRd demonstrated to be effective in RRMM pts treated in real-world setting, without new safety concerns. Better survival outcomes emerged for pts with ≤2 prior lines of therapy, achieving at least a VGPR, and without HRCA.

Keywords: carfilzomib-lenalidomide-dexamethasone; efficacy; multiple myeloma; real-life; relapse; safety.

Publication types

  • Clinical Trial

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Chromosome Aberrations
  • Dexamethasone / administration & dosage
  • Dexamethasone / adverse effects
  • Disease-Free Survival
  • Female
  • Humans
  • Lenalidomide / administration & dosage
  • Lenalidomide / adverse effects
  • Male
  • Middle Aged
  • Multiple Myeloma / drug therapy*
  • Multiple Myeloma / genetics
  • Multiple Myeloma / mortality*
  • Oligopeptides / administration & dosage
  • Oligopeptides / adverse effects
  • Recurrence
  • Survival Rate

Substances

  • Oligopeptides
  • carfilzomib
  • Dexamethasone
  • Lenalidomide

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