Reducing the dose of cytarabine from 800 mg/m2 to 500 mg/m2 allowed a regimen of rituximab, bendamustine, and cytarabine to be safely administered as first-line therapy to elderly patients who had mantle cell lymphoma and were not candidates for autologous stem cell transplant, according to Dr. Carlo Visco of the San Bortolo Hospital in Vicenza, Italy.
“Hematologic toxicity was substantially reduced, compared to the earlier study, Dr. Visco said, calling the R-BAC500 regimen “a highly effective treatment” for patients with mantle cell lymphoma.
Speaking at the at the International Congress on Malignant Lymphoma in Lugano, Switzerland, Dr. Visco noted the “encouraging results, but high hematologic toxicity” seen in a previous study that employed the higher cytarabine dose. In that previous study, transient grades 3-4 thrombocytopenia occurred in 76% of cycles.
In an attempt to reduce hematologic toxicity, the Fondazione Italiana Linfomi designed a phase II trial in which the cytarabine dose was lowered to 500 mg/m2 (R-BAC500). The administration schedule of cytarabine (on days 2-4) and the other components of the original regimen (rituximab, 375 mg/m2, on day 1 and bendamustine, 70 mg/m2, on days 2 and 3) remained unchanged.
The 57 study subjects, median age 71, had newly diagnosed mantle cell lymphoma, and were not eligible for autologous transplant as determined by the comprehensive geriatric assessment; 75% of the patients were males and 91% had Ann Arbor stage III/IV disease.
The Mantle Cell International Prognostic Index (MIPI) was low in 15%, intermediate in 40%, and high in 45%; 9% had the blastoid variant of the disease.
The primary endpoints were complete remission rate, as measured by 18-fluorodeoxyglucose–PET, according to Cheson criteria 2007, and safety. Secondary endpoints included molecular response rate, progression-free survival, and overall survival.
The overall response rate was 96%, and the complete remission rate was 93%. The molecular response rate at the end of treatment was 76% on peripheral blood and 55% on bone marrow samples. With a median follow-up of 18 months, the projected 2-year progression-free survival was 83%, and the overall survival was 91% without maintenance therapy.
Nearly all patients, 53 of 57, received at least four cycles of therapy, and 36 had six cycles. Treatment was discontinued because of toxicity (primarily hematologic) in 15 patients. Only one patient discontinued because of progressive disease.
Grade 3 or 4 neutropenia and thrombocytopenia were observed in about half of administered cycles. Febrile neutropenia occurred in 6%. Extrahematologic toxicity was mainly cardiac (5%).