title: Salvage treatment with lenalidomide and dexamethasone in relapsed/refractory mantle cell lymphoma: clinical results and effects on microenvironment and neo-angiogenic biomarkers.
abstract: BACKGROUND
  Preclinical studies have highlighted the activity of lenalidomide in mantle cell lymphoma and its anti-proliferative synergy with dexamethasone.
  
  
  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).
authors: Clinica Ematologica, Centro Trapianti e Terapie Cellulari Carlo Melzi, Azienda Ospedaliero Universitaria S. M. Misericordia, p.le S. Maria Misericordia 15, 33100 Udine, Italy. zaja.francesco@aoud.sanita.fvg.it
authors: Francesco
authors: F
authors: Zaja
authors: Stefano
authors: S
authors: De Luca
authors: Umberto
authors: U
authors: Vitolo
authors: Lorella
authors: L
authors: Orsucci
authors: Alessandro
authors: A
authors: Levis
authors: Flavia
authors: F
authors: Salvi
authors: Chiara
authors: C
authors: Rusconi
authors: Erika
authors: E
authors: Ravelli
authors: Alessandra
authors: A
authors: Tucci
authors: Chiara
authors: C
authors: Bottelli
authors: Monica
authors: M
authors: Balzarotti
authors: Ercole
authors: E
authors: Brusamolino
authors: Maurizio
authors: M
authors: Bonfichi
authors: Stefano A
authors: SA
authors: Pileri
authors: Elena
authors: E
authors: Sabattini
authors: Stefano
authors: S
authors: Volpetti
authors: Chiara
authors: C
authors: Monagheddu
authors: Angelo
authors: A
authors: Vacca
authors: Roberto
authors: R
authors: Ria
authors: Renato
authors: R
authors: Fanin
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology* / Q000627:therapeutic use*; D015415:Biomarkers / Q000378:metabolism; D003907:Dexamethasone / Q000008:administration & dosage; D005260:Female; D006801:Humans; D000077269:Lenalidomide; D020522:Lymphoma, Mantle-Cell / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D012008:Recurrence; D016879:Salvage Therapy; D013792:Thalidomide / Q000008:administration & dosage / Q000031:analogs & derivatives; D016896:Treatment Outcome; D059016:Tumor Microenvironment / Q000187:drug effects*
chemical_list: D015415:Biomarkers; D013792:Thalidomide; D003907:Dexamethasone; D000077269:Lenalidomide