P666: 1 year results of dasatinib 70mg/day versus 100mg/day in newly diagnosed patients with chronic myeloid leukemia in chronic phase(cml-cp):a prospective randomized controlled study.

Background: Dasatinib 100mg/d first-line for patients with chronic myeloid leukemia has a positive effect, but the side effects cannot be ignored. 2 single-arm phase 2 clinical studies using dasatinib from 100mg/d to 50mg/d were carried out in Japan and the study exploring the optimal trough concentration of dasatinib in South Korea. At present, research on the first-line low-dose dasatinib treatment of CML is in the ascendant. Aims: In this study, we compared the efficacy and adverse effects of dasatinib 70 mg/day versus standard dose 100 mg/day in patients with newly diagnosed CML-CP. Primary endpoints: 12-month rate of complete cytogenetic response (CCyR) and major molecular response (MMR);Secondary endpoints: 1）The proportion of patients who achieved the best efficacy at the 3rd, 6th and 12th months, refer to the ELN guidelines; 2）12-month MMR and MR 4.0 rates; 3）Drug-related hematologic and non-hematologic toxicity analysis. Methods: This is a head-to-head multicenter open-label Phase IV clinical study. A total of 91 patients newly diagnosed with CML-CP Asian from Jul. 2019 to Sep. 2022 were randomly divided into dasatinib 70 mg/d group (N=47) and dasatinib 100 mg/d group (N=44), and the efficacy and adverse events were observed and compared between the two groups. Results: All 91 patients with CML-CP achieved hematologic remission at 3 months of treatment, and the best response, CCyR and MMR rates at 3mos in the 70mg/d group and 100mg/d group were 93.94% vs 88.24%, 60.61% vs 70.59%,15.15% vs 35.29%;At 6 months, the ORR, CCyR, MMR and MR4.0 rates were 92.86% vs 83.87%, 92.86% vs. 83.87%, 53.57% vs 70.97%, 35.71% vs 32.26%; At 9 months, the CCyR, MMR rates and MR4.0 were 94.74% vs 84.00%, 63.16% vs 68.00%, 26.32% vs 44.00%. At 12 months, CCyR, MMR (best response rate), and MR4.0 were 100% vs 100.00%, 83.33% vs 83.33%, 54.17% vs. 58.33%.When the follow-up reached 12 months, CCyR, MMR (also the best response rate), and MR4.0 were 100% vs. 100.00%, 83.33% vs83.33%, 54.17% vs. 58.33%.The most common adverse reactions were 27 cases (57.44%) of anemia grade 1/2, which did not affect the treatment of TKIs; There were 4 cases of pleural effusion, all of which were grade 1-2 adverse reactions, including 8 cases (17.02%) with neutrophil count decreased, 6 cases (12.77%) were depleted, 4 cases (8.51%) were reduced in white blood cell count, and 4 cases (8.51%) were reduced in platelet count.The most common adverse reaction of 44 patients in the 100mg/d group was anemia grade 1/2 in 24 cases (54.55%), which did not affect the treatment of TKI. There were 4 cases (9.09%) of pleural effusion, all of which were grade 1/2; Among the grade 3/4 hematological adverse reactions, the number of white blood cells decreased in 5 cases (11.36%), the number of neutrophils decreased in 10 cases (22.73%), anemia decreased in 5 cases (11.36%), and platelet count decreased in 10 cases (22.73%). Except for the increase in LDH, there was no significant difference in the incidence of AEs between the two groups (P>0.05). Summary/Conclusion: Our study suggests that there was no significant difference in the efficacy and safety of dasatinib 70mg/d and 100mg/d in patients with CML-CP, and the dose-reduced treatment of dasatinib 70mg/d was positive and safe in Asian patients with CML for the first-line treatment. Keywords: Chronic myeloid leukemia