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, 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
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).
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Source: PubMed