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R educed occurrence of tumor flare with flavopiridol followed by combined flavopiridol and lenalidomide in patients with relapsed chronic lymphocytic leukemia (CLL)
Author(s) -
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
Publication year - 2015
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/ajh.23946
Subject(s) - lenalidomide , medicine , chronic lymphocytic leukemia , refractory (planetary science) , gastroenterology , pharmacology , oncology , multiple myeloma , leukemia , biology , astrobiology
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 mg m −2 intravenous bolus (IVB) + 30 mg m −2 continuous intravenous infusion (CIVI) cycle (C) 1 day (D) 1 and 30 mg m −2 IVB + 50 mg m −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. © 2015 Wiley Periodicals, Inc.