A phase IIb trial of vorinostat in combination with lenalidomide and dexamethasone in patients with multiple myeloma refractory to previous lenalidomide-containing regimens

Larysa Sanchez, David H. Vesole, Joshua R. Richter, Noa Biran, Elizabeth Bilotti, Laura McBride, Palka Anand, Kristin Ivanovski, David S. Siegel

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Clinical trials of vorinostat, a Class I/II histone deacetylase inhibitor, in combination with proteasome inhibitors and immunomodulatory agents have shown activity in relapsed/refractory multiple myeloma. This phase IIb, open-label, single-institution study evaluated the efficacy of vorinostat in combination with lenalidomide and dexamethasone in lenalidomide-refractory patients. Patients were considered lenalidomide-refractory if they had no clinical response (<minimal response) on a previous lenalidomide-containing regimen (lenalidomide non-responsive) or if they had progressive disease on or within 60 days of discontinuing a previous lenalidomide-containing regimen (lenalidomide relapsed/refractory). Patients received oral vorinostat 400 mg days 1–7 and 15–21, lenalidomide 25 mg days 1–21, and dexamethasone 40 mg days 1, 8, 15 and 22 in 28-day cycles. Twenty-five patients were enrolled, median age was 65 years and patients had received a median of 5 prior regimens. The overall response rate was 24% (6 partial responses) and clinical benefit rate (≥stable disease) was 80%. Median time to a partial response was 1·9 months and median duration of response was 3·3 months. Median progression-free survival was 5·3 months. Most common grade 3/4 adverse events were neutropenia (48%), thrombocytopenia (32%), anaemia (20%) and gastrointestinal toxicities (16%). In this heavily pre-treated population, vorinostat in combination with lenalidomide and dexamethasone was active in lenalidomide-refractory patients.

Original languageEnglish
Pages (from-to)440-447
Number of pages8
JournalBritish Journal of Haematology
Volume176
Issue number3
DOIs
StatePublished - 1 Feb 2017
Externally publishedYes

Keywords

  • clinical trials
  • lenalidomide
  • multiple myeloma
  • myeloma therapy
  • vorinostat

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