AJH: first-line treatment of CML in the chronic phase, dasatinib 50 mg is not inferior to 100 mg

With the development of a small molecule tyrosine kinase inhibitor (TKI) targeting BCR::ABL1, the therapeutic landscape for chronic myeloid leukemia (CML) has changed dramatically, with 4 different TKIs currently approved for first-line treatment of newly diagnosed CML, including first-line treatment of first-generation TKI imatinib and second-generation TKI dasatinib, nilotinib, and bosutinib
.

Dasatinib is a potent second-generation TKI that produces faster and deeper molecular reactions than imatinib but fails to improve survival
.

To compare outcomes in patients with CML-CP who received a first-line low-dose dasatinib 50 mg/day with a standard dose of dasatinib 100 mg/day, Professor Elias Jabbour, MD Anderson Cancer Center, led a randomized study of 233 patients with CML-CP, which confirmed that dasatinib 50 mg/day was not inferior to 100 mg/day, with better safety features and drug exposure
.

Results of the study

From November 2005 to August 2014, 150 patients with newly diagnosed CML-CP received dasatinib 100 mg/day, and 83 patients received dasatinib 50 mg/day from March 2016 to April 2018, and then matched with a 1:1 propensity score, and the baseline patient characteristics before the propensity score matching are detailed in Table 1
.

Response rate

The overall median follow-up time after matching the propensity score was 60 months: 48 months for the low-dose and 131-month
cohorts for the standard dose, respectively.

Dasatinib 50 mg/day induced a faster response than 100 mg/day, and the median time to CCyR, MR4, and MR4.

Survival ending

In the prematched cohort, dasatinib 50 mg/day tended to improve compared with FFS of 100 mg/day, with 4-year FFS rates of 86% and 76% (p=0.

security

Overall, both cohorts were well
tolerated.

2 patients in the low-dose group (3%) discontinued dasatinib: 1 patient due to bone marrow suppression, 1 patient lost to follow-up; In the standard dose group, 8 patients (10%) discontinued treatment: 2 patients due to gastrointestinal toxicity, 2 patients withdrew consent, 1 patient due to pleural effusion, 1 patient due to bone marrow suppression, 1 patient due to loss of response, and 1 patient lost follow-up
.

discuss

This study is the first report
to compare the clinical outcomes of dasatinib 50 mg/day with the standard dose of dasatinib 100 mg/day in patients with CML-CP.

Overall, dasatinib 50 mg/day should be used as standard treatment
for newly diagnosed CML-CP with at least 100 mg/day efficacy with less toxicity and lower cost.

References

Elias Jabbour,et al.