Intervention Therapy Based on MRD Detected By Flow Cytometry in Peripheral Blood during Early Induction Chemotherapy Could Improve the Remission Rate of Newly Diagnosed Acute Myeloid Leukemia
Authors: Tan Yehui , Yang Yanping , Li Yuying , Qi Sunyao , Gao Sujun 
Published: December 2024

Background: Intensive chemotherapy was the standard induction therapy for young patients with acute myeloid leukemia (AML), but only 60% -80% patients could achieve complete remission. Our previous research has found that the measurable residual disease (MRD) exceeds 0.945% detected by flow cytometry in peripheral blood on day 7 of ND AML who treated with 3+7 regimen could predicted lower remission rate.

Objective: To evaluate the efficacy of early intervention guided by 7th day chemotherapy peripheral blood MRD detected by flow cytometry in ND AMLpatients.

Method: Patients who received “7+3” regimen therapy at the Hematology Department of the First Affiliated Hospital of Jilin University from January 2023 to December 2023 and with peripheral blood MRD≥1% on 7th day were retrospective analyzed. The cCR (CR+CRi+MLFS) was compared between patients who received intervention based on 7th day peripheral blood MRD and those who did not. Intervention therapy was based on whether there was a FLT3-ITD mutation and MRD level. For patients with FLT-ITD and MRD≥1%, Gilteritinib 80mg was orally administrated on days 8-21, for patients with FLT3-ITD negative, MRD≥1% and&lt;10%, venetoclax 400 mg was orally administrated on day 8-14, for Patients with FLT3-ITD negative and MRD≥10%, venetoclax 400mg was orally administrated on day day 8-21 plus with azacitidine 75mg/m2 subcutaneously administrated on day 8-14. The Bone marrow morphological evaluation was performed on day 28 after chemotherapy. The Kaplan-Meier was employed for survival analysis, and the log-rank test was used to compare the cCR and adverse events between the intervention and no intervention groups.

Result: A total of 23 Chinese patients were included (13 males and 10 females). The median age of 12 non intervention patients was 39.5 (15-57) years, with 4 cases (33%) in the high-risk ELN group, 2 cases (17%) in the medium risk group, and 6 cases (50%) in the low-risk group; The median peripheral blood MRD of D7 was 3.695 (1.21-49.54)%; The median age of 11 patients in the intervention group was 35 (14-59) years old, with 6 cases in the high-risk group (55%), 5 cases in the medium risk group (45%), and none in low-risk group. The median peripheral blood MRD of D7 was 12.69 (1.45-79.33)%, among which 6 patients (55%) had MRD≥10%. There was no statistically significant difference in clinical characteristics between the two groups. In the intervention group, 3 patients were treated with Gilteritinib, while the remaining 8 patients were treated with venetoclax±azacitidine. The cCR (CR+CRI+MLFS) of the intervention group was significantly higher than that of the non intervention group (9/11, 82% vs 4/12, 33%, P=0.0191). The overall response rate (ORR) of the intervention group reached 91% (10/11), while that of the non intervention group was 58% (7/12); Nine patients (82%) in the intervention group recovered their neutrophil count and platelet count, with median recovery times of 25 days for absolute neutrophil count (ANC&gt;500/μ L) and 20 days for platelet count (&gt;50 x 109/L). Seven patients (75%) in the non intervention group recovered their neutrophil count (ANC&gt;500/μ L) and platelet count (&gt;50 x 109/L), with median recovery times of 17 days and 15.5 days, respectively. There was no significant difference in non hematological adverse events between the two groups. In the intervention group, the grade 3 or above non hematological adverse events including pneumonia (91%), neutropenia with fever (82%), sepsis (45%), and skin allergic reactions (27%); In the non intervention group, neutropenia with fever (67%), sepsis (33%), and skin allergic reactions (25%) were included. During the median follow-up period of 12.1 months, eight patients in the non intervention group and two patients in the intervention group died.The median survival of the non intervention group was 12.1 months compared to the the median survival was not reach of the intervention group (p=0.1685).

Conclusion: Early intervention therapy guided by peripheral blood MRD on the 7th day of induction chemotherapy could significantly improve the cCR of AML patients and there is no significant increased adverse events.