Dasatinib in imatinib‐resistant or imatinib‐intolerant chronic myeloid leukemia in blast phase after 2 years of follow‐up in a phase 3 study

Abstract

BACKGROUND In a phase 3 study, the authors assessed the effects of dasatinib at doses of 140 mg once daily and 70 mg twice daily in patients who had either chronic myeloid leukemia (CML) in advanced phases or Philadelphia chromosome-positive acute lymphoblastic leukemia and were resistant or intolerant to imatinib. In the current report, the results for patients with CML in blast phase after 2 years of follow-up are reported. METHODS Patients were stratified according to whether they had CML in myeloid blast phase (MBP-CML) or in lymphoid blast phase (LBP-CML) and were randomized (1:1) within each stratum to receive either oral dasatinib 140 mg once daily or 70 mg twice daily. RESULTS In patients with MBP-CML, the major hematologic response rate was 28% for both regimens; and, in patients with LBP-CML, the major hematologic response rate was 42% for once-daily dasatinib and 32% for twice-daily dasatinib. The major cytogenetic response rates were 25% for once-daily dasatinib and 28% for twice-daily dasatinib in patients with MBP-CML, and the respective rates in patients with LBP-CML were 50% and 40%. The overall survival rate at 24 months was 24% for once-daily dasatinib and 28% for twice-daily dasatinib in patients with MBP-CML, and the respective values in patients with LBP-CML were 21% and 16%. Adverse events indicated a trend toward improved tolerability for the once-daily regimen. CONCLUSIONS The current results suggested that dasatinib 140 mg once daily had similar efficacy and improved tolerability relative to the 70-mg twice-daily regimen in patients with imatinib-resistant, blast phase CML.

Allogeneic hematopoietic SCT in combination with tyrosine kinase inhibitor treatment compared with TKI treatment alone in CML blast crisis

“…Second-generation TKIs can rapidly reduce leukemia burden and induce an improved response rate in BC. 6,7 Therefore, an initial therapy with second-generation TKIs might induce early and durable CCyR and MMR, and improve long-term survival in CML-BC. 31 Whether allo-HSCT is superior to second-generation TKIs for CML-BC not treated with imatinib remains an issue for future study.…”

“…5 Furthermore, similar responses were reported in patients with imatinib-resistant CML-BC after the treatment with second generation TKIs (nilotinib and dasatinib), the 24-month OS is 21-27%. [6][7][8] Thus, TKI treatment alone has not improved longterm survival in patients with CML-BC.…”

Monitoring disease burden in chronic myeloid leukemia: Past, present, and future

“…In general, response correlates with the disease phase, and the best responses (and, thus, lowest rates of resistance) are observed in patients with newly diagnosed chronic-phase CML with a low Sokal score, and the poorest responses are observed in patients in blast crisis [34][35][36][37]. In roughly 50% of patients with secondary resistance, base pair mutations in the ABL1 kinase domain blunt the ability of the TKI to inhibit the aberrant BCR-ABL1 kinase activity [14].…”

Second Generation Tyrosine Kinase Inhibitors Combined With Allogeneic Hematopoietic Stem Cell Transplantation Improve the Prognosis of Patients with Chronic Myelogenous Leukemia in Blast Crisis

“…Even the achievement of complete hematologic remission (CHR) with imatinib before transplantation does not improve the prognosis of CML in BC, probably due to the frequent development of imatinib resistance in BC [2]. Second-generation tyrosine kinase inhibitors (TKIs-II) alone induce CCyR in 20-40% of patients [3,4]. However, the majority of these patients relapse within 1 year, and the median survival is only 8 months [4].…”

“…Second-generation tyrosine kinase inhibitors (TKIs-II) alone induce CCyR in 20-40% of patients [3,4]. However, the majority of these patients relapse within 1 year, and the median survival is only 8 months [4]. Thus, although TKIs-II is an effective agent in this setting, it is necessary to improve these results.…”