Interferon-a-2b As a Maintenance Therapy Significantly Improves Disease-Free Survival in Patients with Low-Risk Acute Myeloid Leukemia

Background: Interferon-𝜶has a world-widely acknowledged anti-tumor activity and immunoregulatory function. Rare of the previous study reported significant efficacy of IFN-𝜶in AML (high, medium and low risk) patients. Although cytotoxic chemotherapy significantly improved the survival of low-risk AML, the reported low-risk AML 5-year OS was only 34-65%.Whether Interferon-𝜶-2b(IFN-𝜶-2b) could reduce recurrence and improve DFS in the maintenance therapy of low-risk AML subtypes has not been verified. The aim of this study was to evaluate the efficacy and safety of IFN-𝜶-2b in the maintenance of low-risk acute myeloid leukemia, in order to provide suggestions for clinical practice.

Method: This study retrospectively analyzed 31 patients with low-risk AML who were treated with IFN-𝜶-2b maintenance therapy from March 2015 to March 2018 at the Peking University Institute of Hematology. The control group consisted of 1:1 matched 31 patients with low-risk AML. The pairing factors were age, gender, diagnostic time and subtype, induction and consolidation courses, and minimal residual disease (MRD) at the end of chemotherapy. Both groups of patients were AML patients who underwent 1-2 therapeutic induction chemotherapy for complete hematologic remission (CR) and completed 5-7 courses of consolidation chemotherapy. The interferon group was administered with 3 million U ofIFN-𝜶-2b three times a week; the control group was only observed and followed up after consolidation chemotherapy. We compared the treatment efficacy and prognostic improvement in low-risk AML by comparing MRD, disease-free survival (DFS), event-free survival (EFS), and overall survival (OS).

Results: The median age of the 31 patients in the interferon group was 50 (21-67) years. Themolecular biological characteristicsof the interferon group were NPM1+/FLT3-ITD-8 cases; CEBPA double mutation 9 cases; CBFβ-MYH11+/C-KIT-5 cases; and ETO+/C-KIT- 9 cases. The median age of the control group was 44 (26-70) years old, and the molecular biological characteristics were paired with the interferon group. The median follow-up time of the 31 patients with low-risk AML in the interferon group and the control group was 14.5 (4-34) months and 16 (5.5-35) months, respectively. The median duration of treatment in the interferon group was 10(1-24) months. In interferongroup, patients with negative or positive MRD status were 16 and 15, respectively. Whereas, in control group, patients with negative or positive MRD status were 20 and 11, respectively. In interferon group, patients with original MRD, 10/15 (66.67%) showed MRD conversion after the median time of 5 (1-14.5) months IFN-𝜶-2b treatment, while in control group 3/11 (27.3%) of the patients showed MRD negative-positive conversion. There was a statistically significant difference in the rate of MRD conversion between the two groups (X2=3.939, P=0.047). The interferon group significantly decreased the rate of MRD compared with the control group. The conversion rate of the interferon group and the control group was (66.67%) vs (27.3%). In addition, the 2-year EFS of the interferon group was significantly higher than that of the control group (81.6±7.5) % vs (50.0±10.9) %, P=0.041(Figure 1.A). With refer to recurrence, 3 patients had hematologic recurrence in the interferon group, compared with 10 in the control group. Each group has 2 persistent MRD positive patients and MRD level increased more than 2 log-fold. 1 patient in control group had negative MRD converted to positive. The 2-year DFS of the interferon group was significantly higher than that of the control group (81.2±8.8)% vs (56.7±9.9)%, P=0.042 (Figure 1.B). There was no significant difference between the interferon group and the control group at 2 years of OS, which was (91.4±5.8)% vs (78.7±10.8)% (P=0.587) (Figure 1.C).In terms of safety, 24/31 (77.4%) had grade 1-2 fever after IFN-𝜶-2b therapy. 4/31 patients (12.9%) developed grade 3-4 hematologic toxicity, all of which were thrombocytopenia.

Conclusion:IFN-𝜶-2b as maintenance therapyfor CR1 patients with low-risk AML significantly improved the rate of MRD conversion compared with patients without it. DFS and EFS were higher than those without it. Patients receiving interferon therapy have a low incidence of adverse reactions. Interferon therapy is safe and well-tolerated.

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