关键词: 尼洛替尼, 慢性粒细胞白血病, 早期分子学反应, 影响因素

Abstract: Objective To evaluate and analyze the clinical EMR (early molecular response) efficacy of nilotinib in first-line treatment of chronic myeloid leukemia (CML), and to explore the related factors affecting the efficacy of deep EMR; Methods Retrospective analysis was made on 45 patients with chronic myeloid leukemia in the chronic phase admitted to the hematology department of our hospital from December 2016 to December 2020, who were all given nilotinib first-line treatment. Peripheral blood samples were collected at 3 and 6 months after treatment to detect BCR/ABLIS levels to evaluate the deep EMR molecular reaction, record the occurrence of adverse reactions, and follow up to December 2021 to record the progression free survival period; The clinical data of patients were collected and the influencing factors of deep EMR were analyzed; Results The EMR response rate (early molecular biological response: BCR/ABLIS molecular level lower than 10% in 3 months, BCR/ABLIS molecular level lower than 1% in 6 months, and BCR/ABLIS molecular level lower than 0.1% in 12 months) was 82.3%, 92.1%, 86.2% respectively after the first line treatment of nilotinib for 3, 6, and 12 months, and the non-obtained EMR was 17.7% and 7.9% respectively after the first line treatment of nilotinib for 3 and 6 months; The depth of EMR (BCR/ABLIS molecular level was lower than 1% at 3 months and lower than 0.1% at 6 months) was 68.6% and 50.9%, respectively after the first line treatment of nilotinib for 3 and 6 months. At 12 months of treatment, the rate of major molecular response (MMR, BCR/ABLIS level ≤ 0.1%) was 44 cases (86.2%); The median time to reach MMR was 4 (3-17) months; Adverse reactions: neutropenia (4.4%), thrombocytopenia (6.7%), anemia (2.2%), all of which are grade 1 to 2, can be recovered in a short time without grade 3 to 4 hematological adverse reactions; The non hematological adverse reactions were skin rash (4.4%), pruritus (4.4%), nausea (2.2%), which were tolerable and could be relieved after symptomatic treatment without changing the drug dosage; Survival: The progression free survival rate was 98% (50/51); The results of univariate analysis showed that the course of disease before nilotinib, platelet count, hemoglobin, peripheral blood primitive cells and the length of subcostal spleen were all related to the depth of EMR obtained by CML patients, and the difference was statistically significant (P<0.05, see Table 1); The above clinical parameters were introduced into the multifactor Logistic regression analysis model, and the results showed that only the presence of primitive cells in peripheral blood and megasplenomegaly (≥ 7cm under splenic rib) were independent risk factors for patients to obtain deep EMR, P<0.05. Conclusion The efficacy of deep EMR is an important indicator in the era of treatment free remission (TFR) for CML patients. Nilotinib can obtain a high proportion of deep EMR in the first-line treatment of chronic myeloid leukemia, with high safety; The presence of primitive cells in peripheral blood and splenomegaly were independent risk factors for patients to obtain deep EMR.

Key words: Nilotinib, Chronic Myeloid Leukemia, Early Molecular Response, Influencing Factors