Salvage treatment with lenalidomide and dexamethasone in relapsed/refractory mantle cell lymphoma: clinical results and effects on microenvironment and neo-angiogenic biomarkers

Haematologica. 2012 Mar;97(3):416-22. doi: 10.3324/haematol.2011.051813. Epub 2011 Nov 4.

Abstract

Background: Preclinical studies have highlighted the activity of lenalidomide in mantle cell lymphoma and its anti-proliferative synergy with dexamethasone.

Design and methods: In this prospective, multicenter, phase II study, patients with relapsed/refractory mantle cell lymphoma who were not eligible for, or had relapsed after, intensive treatments received lenalidomide 25 mg/day (days 1-21 of each 28-day cycle) and dexamethasone (40 mg/day on days 1, 8, 15, and 22) for up to 12 months.

Results: The primary end-points, overall and complete response rates, were achieved by 17 of 33 (52%; 95% confidence interval [CI], 35-68%) and 8 of 33 patients (24%; 95% CI, 13-41%), respectively, by the end of treatment. Fifteen patients (45%) discontinued treatment prematurely, 13 due to lack of response. The median progression-free and overall survival were 12 months (95% CI, 5-19 months) and 20 months (95% CI, 12 months to not estimable), respectively. Treatment resulted in a significant increase in microvessel density (P=0.033) and non-significant increases in macrophage and natural killer cell counts, while serum levels of neoangiogenic factors did not change significantly. Grade 3/4 adverse events were neutropenia (53%), leukopenia (25%), thrombocytopenia (22%), infections (12%), and febrile neutropenia (12%).

Conclusions: These results confirm a favorable safety and activity profile of lenalidomide in relapsed/refractory mantle cell lymphoma. The contribution of dexamethasone in achieving these results is unclear because of its possible detrimental effect on the immune activation generated by lenalidomide and a higher risk of developing infectious complications. (clinicaltrials.gov identifier: NCT00786851).

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers / metabolism
  • Dexamethasone / administration & dosage
  • Female
  • Humans
  • Lenalidomide
  • Lymphoma, Mantle-Cell / drug therapy*
  • Lymphoma, Mantle-Cell / mortality
  • Male
  • Middle Aged
  • Neovascularization, Pathologic / metabolism*
  • Recurrence
  • Salvage Therapy*
  • Thalidomide / administration & dosage
  • Thalidomide / analogs & derivatives
  • Treatment Outcome
  • Tumor Microenvironment / drug effects*

Substances

  • Biomarkers
  • Thalidomide
  • Dexamethasone
  • Lenalidomide

Associated data

  • ClinicalTrials.gov/NCT00786851