Lenalidomide in Combination With Vorinostat and Dexamethasone for the Treatment of relapsed/refractory Peripheral T Cell Lymphoma (PTCL): Report of a Phase I/II Trial

Ann Hematol. 2014 Mar;93(3):459-62. doi: 10.1007/s00277-014-2009-0. Epub 2014 Jan 18.

Abstract

Given the poor outcome of relapsed and refractory peripheral T cell lymphoma (PTCL), we explored a combination of lenalidomide, vorinostat, and dexamethasone to test the feasibility of this therapy in relapsed and refractory PTCL. Eight patients were accrued: two peripheral T cell lymphoma, unspecified; five angioimmunoblastic T cell lymphoma; and one ALK-negative anaplastic large-cell lymphoma. A dose escalation of lenalidomide (days 1-21, q28) was planned using a 3 + 3 design. As two patients treated with 10 mg/day experienced dose-limiting toxicity (thrombocytopenia grade 3, stroke grade 4), the primary end point of our trial was reached; the maximal tolerable dose of lenalidomide was 5 mg/day (level -I). Adverse events grade ≥3 were observed as thrombocytopenia (23 %), leukocytopenia (15 %), anemia (8 %), and neutropenia (8 %). One complete remission (10.3 months), one partial remission (11.3 months), one stable disease (11.9 months), and four progressive disease (overall response rate 25 %) were observed. The median progression-free survival was 2.2 months and the median OS was 6.7 months. In conclusion, the poor results obtained with lenalidomide in combination with vorinostat and dexamethasone provide no arguments that could justify further investigation of this drug combination for the treatment of relapsed PTCL.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Angiogenesis Inhibitors / administration & dosage
  • Angiogenesis Inhibitors / therapeutic use
  • Antineoplastic Agents, Hormonal / administration & dosage
  • Antineoplastic Agents, Hormonal / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Cohort Studies
  • Dexamethasone / administration & dosage
  • Dexamethasone / therapeutic use*
  • Drug Resistance, Neoplasm
  • Feasibility Studies
  • Female
  • Histone Deacetylase Inhibitors / administration & dosage
  • Histone Deacetylase Inhibitors / therapeutic use
  • Humans
  • Hydroxamic Acids / administration & dosage
  • Hydroxamic Acids / therapeutic use*
  • Lenalidomide
  • Lymphoma, Large-Cell, Anaplastic / drug therapy
  • Lymphoma, Large-Cell, Anaplastic / pathology
  • Lymphoma, Large-Cell, Immunoblastic / drug therapy
  • Lymphoma, Large-Cell, Immunoblastic / pathology
  • Lymphoma, T-Cell, Peripheral / drug therapy*
  • Lymphoma, T-Cell, Peripheral / pathology
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Recurrence
  • Survival Analysis
  • Thalidomide / administration & dosage
  • Thalidomide / analogs & derivatives*
  • Thalidomide / therapeutic use
  • Thrombocytopenia / chemically induced
  • Vorinostat

Substances

  • Angiogenesis Inhibitors
  • Antineoplastic Agents, Hormonal
  • Histone Deacetylase Inhibitors
  • Hydroxamic Acids
  • Thalidomide
  • Vorinostat
  • Dexamethasone
  • Lenalidomide