HemaSphere (Oct 2022)

Carfilzomib, Pomalidomide, and Dexamethasone As Second-line Therapy for Lenalidomide-refractory Multiple Myeloma

  • Pieter Sonneveld,
  • Sonja Zweegman,
  • Michele Cavo,
  • Kazem Nasserinejad,
  • Annemiek Broijl,
  • Rosella Troia,
  • Ludek Pour,
  • Sandra Croockewit,
  • Paolo Corradini,
  • Francesca Patriarca,
  • Kalung Wu,
  • Jolanda Droogendijk,
  • Gerard Bos,
  • Roman Hajek,
  • Maria Teresa Petrucci,
  • Paula Ypma,
  • Nicholas Zojer,
  • Monique C. Minnema,
  • Mario Boccadoro

DOI
https://doi.org/10.1097/HS9.0000000000000786
Journal volume & issue
Vol. 6, no. 10
p. e786

Abstract

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This phase 2 trial investigated reinduction with carfilzomib, pomalidomide, and dexamethasone (KPd) and continuous pomalidomide/dexamethasone in patients at first progression during lenalidomide maintenance. The second objective was to evaluate high-dose melphalan with autologous stem cell transplantation (HDM/ASCT) at first progression. Patients were eligible who had progressive disease according to International Myeloma Working Group (IMWG) criteria. Treatment consisted of 8 cycles carfilzomib (20/36 mg/m2), pomalidomide (4 mg) and dexamethasone. Patients without prior transplant received HDM/ASCT. Pomalidomide 4 mg w/o dexamethasone was given until progression. One hundred twelve patients were registered of whom 86 (77%) completed 8 cycles of KPd. Thirty-five (85%) eligible patients received HDM/ASCT. The median time to discontinuation of pomalidomide w/o dexamethasone was 17 months. Best response was 37% ≥ complete response, 75% ≥ very good partial response, 92% ≥ partial response, respectively. At a follow-up of 40 months median PFS was 26 and 32 months for patients who received KPd plus HDM/ASCT and 17 months for patients on KPd (hazard ratio [HR] 0.61, 95% confidence interval [CI] 0.37-1.00, P = 0.051). PFS was better after longer duration of prior lenalidomide (HR 3.56, 95% CI 1.42-8.96, P = 0.035). Median overall survival (OS) was 67 months. KPd-emerging grade 3 and 4 adverse events included hematologic (41%), cardiovascular (6%), respiratory (3%), infections (17%), and neuropathy (2%). KPd followed by continuous pomalidomide is an effective and safe triple drug regimen in second-line for patients previously exposed to bortezomib and/or refractory to lenalidomide.