Despite improvements in standard therapy with rituximab-cyclophosphamide-doxorubicin- vincristine-prednisone scheme for patients with untreated, diffuse large-B-cell lymphoma up to 40% relapse. Lenalidomide alone or in combination with rituximab showed activity in relapsed/refractory aggressive lymphomas. In this phase I study we determined the maximum tolerated dose of lenalidomide plus rituximab-cyclophosphamide-doxorubicin-vincristine- prednisone in untreated elderly (median age 68 years) patients with diffuse large-B-cell lymphoma. Four lenalidomide doses (5, 10, 15, and 20 mg/day on days 1-14) allocated using the continual reassessment method were planned to be administered for 14 days in combination with each course of rituximab-cyclophosphamide-doxorubicin-vincristine-prednisone for a total of six courses. Seven patient cohorts (n=3 each) were treated (total n=21) at 10, 20, 15, 15, 15, 10, and 10 mg of lenalidomide. Dose-limiting toxicities occurred in seven patients during the first three treatment courses. The third dose-level of lenalidomide (15 mg/day) was selected as the maximum tolerated dose, with an estimated dose-limiting toxicities probability of 0.345 (95% credibility interval 0.164-0.553). Grade 3-4 hematologic adverse events were: neutropenia in 28% of the courses, thrombocytopenia in 9%, and anemia in 3%. Non-hematologic toxicities were moderate: grade 4 increase of creatinine phosphokinase (n=1), grade 3 cardiac (n=2), grade 3 neurologic (n=3), and grade 3 gastrointestinal (n=1). In this phase I study, 90% of patients achieved an overall response with 81% achieving complete remission. This combination regimen appears safe in elderly patients with diffuse large-B-cell lymphoma and its efficacy will be assessed in the ongoing phase II trial. This trial was registered at www.clinicaltrials.gov as NCT00907348.
Lenalidomide plus cyclophosphamide, doxorubicin, vincristine, prednisone and rituximab is safe and effective in untreated elderly diffuse large B-cell lymphoma patients: phase I study by the Fondazione Italiana Linfomi.
BALDI, ILEANA;
2013
Abstract
Despite improvements in standard therapy with rituximab-cyclophosphamide-doxorubicin- vincristine-prednisone scheme for patients with untreated, diffuse large-B-cell lymphoma up to 40% relapse. Lenalidomide alone or in combination with rituximab showed activity in relapsed/refractory aggressive lymphomas. In this phase I study we determined the maximum tolerated dose of lenalidomide plus rituximab-cyclophosphamide-doxorubicin-vincristine- prednisone in untreated elderly (median age 68 years) patients with diffuse large-B-cell lymphoma. Four lenalidomide doses (5, 10, 15, and 20 mg/day on days 1-14) allocated using the continual reassessment method were planned to be administered for 14 days in combination with each course of rituximab-cyclophosphamide-doxorubicin-vincristine-prednisone for a total of six courses. Seven patient cohorts (n=3 each) were treated (total n=21) at 10, 20, 15, 15, 15, 10, and 10 mg of lenalidomide. Dose-limiting toxicities occurred in seven patients during the first three treatment courses. The third dose-level of lenalidomide (15 mg/day) was selected as the maximum tolerated dose, with an estimated dose-limiting toxicities probability of 0.345 (95% credibility interval 0.164-0.553). Grade 3-4 hematologic adverse events were: neutropenia in 28% of the courses, thrombocytopenia in 9%, and anemia in 3%. Non-hematologic toxicities were moderate: grade 4 increase of creatinine phosphokinase (n=1), grade 3 cardiac (n=2), grade 3 neurologic (n=3), and grade 3 gastrointestinal (n=1). In this phase I study, 90% of patients achieved an overall response with 81% achieving complete remission. This combination regimen appears safe in elderly patients with diffuse large-B-cell lymphoma and its efficacy will be assessed in the ongoing phase II trial. This trial was registered at www.clinicaltrials.gov as NCT00907348.Pubblicazioni consigliate
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