Haematologica (Mar 2012)

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

  • Francesco Zaja,
  • Stefano De Luca,
  • Umberto Vitolo,
  • Lorella Orsucci,
  • Alessandro Levis,
  • Flavia Salvi,
  • Chiara Rusconi,
  • Erika Ravelli,
  • Alessandra Tucci,
  • Chiara Bottelli,
  • Monica Balzarotti,
  • Ercole Brusamolino,
  • Maurizio Bonfichi,
  • Stefano A. Pileri,
  • Elena Sabattini,
  • Stefano Volpetti,
  • Chiara Monagheddu,
  • Angelo Vacca,
  • Roberto Ria,
  • Renato Fanin

DOI
https://doi.org/10.3324/haematol.2011.051813
Journal volume & issue
Vol. 97, no. 3

Abstract

Read online

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).