TY - JOUR
T1 - Salvage treatment with lenalidomide and dexamethasone in relapsed/refractory mantle cell lymphoma
T2 - Clinical results and effects on microenvironment and neo-angiogenic biomarkers
AU - Zaja, Francesco
AU - De Luca, Stefano
AU - Vitolo, Umberto
AU - Orsucci, Lorella
AU - Levis, Alessandro
AU - Salvi, Flavia
AU - Rusconi, Chiara
AU - Ravelli, Erika
AU - Tucci, Alessandra
AU - Bottelli, Chiara
AU - Balzarotti, Monica
AU - Brusamolino, Ercole
AU - Bonfichi, Maurizio
AU - Pileri, Stefano A.
AU - Sabattini, Elena
AU - Volpetti, Stefano
AU - Monagheddu, Chiara
AU - Vacca, Angelo
AU - Ria, Roberto
AU - Fanin, Renato
PY - 2012/3/1
Y1 - 2012/3/1
N2 - 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.
AB - 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.
KW - Dexamethasone
KW - Lenalidomide
KW - Mantle cell lymphoma
KW - Relapsed/refractory disease
KW - Salvage treatment
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U2 - 10.3324/haematol.2011.051813
DO - 10.3324/haematol.2011.051813
M3 - Article
C2 - 22058200
AN - SCOPUS:84857740069
VL - 97
SP - 416
EP - 422
JO - Haematologica
JF - Haematologica
SN - 0390-6078
IS - 3
ER -