Flavopiridol, Fludarabine, and Rituximab in Mantle Cell Lymphoma and Indolent B-Cell Lymphoproliferative Disorders

作者：Lin Thomas S; Blum Kristie A; Fischer Diane Beth; Mitchell Sarah M; Ruppert Amy S; Porcu Pierluigi; Kraut Eric H; Baiocchi Robert A; Moran Mollie E; Johnson Amy J; Schaaf Larry J; Grever Michael R; Byrd John C^*

来源：Journal of Clinical Oncology, 2010, 28(3): 418-423.

DOI：10.1200/JCO.2009.24.1570

Purpose
Flavopiridol downmodulates antiapoptotic proteins associated with resistance to fludarabine and rituximab and is effective against p53-mutated chronic lymphocytic leukemia (CLL). We conducted a phase I study of flavopiridol, fludarabine, and rituximab (FFR) in patients with mantle-cell lymphoma (MCL), indolent B-cell non-Hodgkin's lymphomas (B-NHL), and CLL to determine the activity of FFR.
Patients and Methods
Therapy included fludarabine 25 mg/m(2) intravenously (IV) days 1 to 5 and rituximab 375 mg/m(2) day 1 every 28 days for 6 cycles. We administered flavopiridol 50 mg/m(2) by 1-hour IV bolus (IVB) day 1 (n = 15); day 1 to 2 (n = 6); 20 mg/m(2) 30-minute IVB = 20 mg/m(2) 4-hour IV infusion (n = 3); or 30 mg/m(2) = 30 mg/m(2) (n = 14).
Results
Thirty-eight patients (median age, 62 years) with MCL (n = 10); indolent B-NHL including follicular (n = 9), marginal zone (n = 4), lymphoplasmacytic (n = 1), or small lymphocytic lymphoma (n = 3); and CLL (n = 11), were enrolled. Twenty-two patients were previously untreated; 16 had received one to two prior therapies. Two patients in cohort 2 developed grade 3 dose-limiting toxicity (seizures, renal insufficiency). The median number of treatment cycles was 4, with cytopenias (n = 10) and fatigue (n = 3) the most common reasons for early discontinuation. Overall response rate was 82% (complete response, 50%; unconfirmed complete response, 5%; partial response, 26%), including 80% of patients with MCL (median age, 68; seven complete responses, one partial response). Median progression-free survival (PFS) was 25.6 months. Median PFS of patients with nonblastoid variant MCL (n = 8) was 35.9 months.
Conclusion
FFR was active in MCL, indolent B-NHL, and CLL and should be studied for older patients with MCL who are not candidates for aggressive chemotherapy.

• 出版日期2010-1-20