Phase Ib/II trial of CYKLONE (cyclophosphamide, carfilzomib, thalidomide and dexamethasone) for newly diagnosed myeloma

Joseph R. Mikhael, Craig B. Reeder, Edward N. Libby, Luciano J. Costa, P. Leif Bergsagel, Francis Buadi, Angela Mayo, Sravan K. Nagi Reddy, Katherine Gano, Amylou C. Dueck, A. Keith Stewart

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42 Scopus citations

Abstract

Sixty-four transplant-eligible patients with newly diagnosed multiple myeloma (NDMM) received carfilzomib (days 1, 2, 8, 9, 15, 16), 300 mg/m2 cyclophosphamide (days 1, 8, 15), 100 mg thalidomide (days 1-28) and 40 mg dexamethasone (days 1, 8, 15, 22) in 28-day cycles (CYKLONE regimen). Carfilzomib was dose-escalated to 15/20, 20/27, 20/36 and 20/45 mg/m2 to determine the maximum tolerated dose (MTD), which was 20/36 mg/m2. Regardless of attribution, common Grade 3 or higher adverse events were lymphopenia (38%), neutropenia (23%) and anaemia (20%). All peripheral neuropathy (31%) was Grade 1 and considered most likely to be thalidomide-related. Common cardiac or pulmonary events of any grade in ≥5% of patients included dyspnoea (20%) and cough (6%). Overall (N = 64), 91% of patients achieved a best response of partial response or better across all cycles of treatment, including five patients with complete responses. At the MTD (n = 29), 59% of patients achieved a very good partial response or better after four cycles (primary end point). Stem cell collection was successful in all patients in whom it was attempted (n = 42). Progression-free survival and overall survival at 24 months was 76% and 96%, respectively (median follow-up of 17·5 months). CYKLONE appears highly efficacious in NDMM patients, with manageable toxicities.

Original languageEnglish (US)
Pages (from-to)219-227
Number of pages9
JournalBritish journal of haematology
Volume169
Issue number2
DOIs
StatePublished - Apr 1 2015

Keywords

  • Clinical studies
  • Clinical trials
  • Experimental therapies
  • Multiple myeloma
  • Myeloma therapy

ASJC Scopus subject areas

  • Hematology

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