Association of lymphocytosis following treatment with dasatinib with response and outcome.

Abstract

6553 Background: Persistent clonal expansion of cytotoxic T or NK cells has been described in patients with CML and Ph+ ALL during dasatinib therapy. Methods: Data from phase II and III trials of dasatinib were used to conduct a large analysis in all phases of CML after 2 years of therapy. Rates of major (MCyR) and complete (CCyR) cytogenetic response, progression-free survival (PFS: loss of complete hematologic response or MCyR or death; advanced-phase disease: the same or increasing white-blood cells), and adverse events (AEs) were measured in those with and without lymphocytosis (defined as lymphocytes >3.6 x 109/L on ≥2 occasions after 20 days of treatment). Results: Lymphocytosiswas observed in a large proportion of dasatinib-treatedpatients in chronic (31%), accelerated (39%), and myeloid blast (34%) phase. The incidence of lymphocytosis was similar in patients in chronic phase receiving total doses of 100 or 140 mg of dasatinib. Rates of CCyR were higher in patients with lymphocytosis, especially among those with advanced-phase CML (Table). Longer median PFS was observed in patients with advanced disease and lymphocytosis, but not among those in chronic phase. Rates of overall AEs were similar between patients with and without detectable lymphocytosis, including rates of AEs associated with inflammation. Conclusions: Lymphocytosis occurs commonly after treatment with dasatinib and is associated with improved cytogenetic response and longer PFS, suggesting that some of the antileukemic effects of dasatinib may be associated with immune activation. Future studies, including immunological characterization of the lymphocytes and their possible targets, will be of considerable interest. CML phase n Lymphocytosis (%) MCyR (%) CCyR (%) Median PFS (m) Chronic 1,150 Yes (31) 70 58 30 No (69) 58 49 >31 Accelerated 490 Yes (39) 52 44 28.6 No (61) 34 26 20.3 Myeloid blast 257 Yes (34) 38 32 6.9 No (66) 28 18 3.5 Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb Bristol-Myers Squibb, Chemgenix, Merck, Novartis, Wyeth Bristol-Myers Squibb, Novartis Bristol-Myers Squibb, Merck, Novartis Bristol-Myers Squibb, Novartis