Reduced occurrence of tumor flare with flavopiridol followed by combined flavopiridol and lenalidomide in patients with relapsed chronic lymphocytic leukemia (CLL)

作者：Maddocks Kami^*; Wei Lai; Rozewski Darlene; Jiang Yao; Zhao Yuan; Adusumilli Mikhil; Pierceall William E; Doykin Camille; Cardone Michael H; Jones Jeffrey A; Flynn Joseph; Andritsos Leslie A; Grever Michael R; Byrd John C; Johnson Amy J; Phelps Mitch A; Blum Kristie A

来源：American Journal of Hematology, 2015, 90(4): 327-333.

DOI：10.1002/ajh.23946

Flavopiridol and lenalidomide have activity in refractory CLL without immunosuppression or opportunistic infections seen with other therapies. We hypothesized that flavopiridol treatment could adequately de-bulk disease prior to lenalidomide therapy, decreasing the incidence of tumor flare with higher doses of lenalidomide. In this Phase I study, the maximum tolerated dose was not reached with treatment consisting of flavopiridol 30 mgm(-2) intravenous bolus (IVB)+30 mgm(-2) continuous intravenous infusion (CIVI) cycle (C) 1 day (D) 1 and 30 mgm(-2) IVB+50 mgm(-2) CIVI C1 D8,15 and C2-8 D3,10,17 with lenalidomide 15 mg orally daily C2-8 D1-21. There was no unexpected toxicity seen, including no increased tumor lysis, tumor flare (even at higher doses of lenalidomide) or opportunistic infection. Significant clinical activity was demonstrated, with a 51% response rate in this group of heavily pretreated patients. Biomarker testing confirmed association of mitochondrial priming of the BH3 only peptide Puma with response.Am. J. Hematol. 90:327-333, 2015.

• 出版日期2015-4