Maintenance Therapy with Combination of Azacitidine, Danazol and Thalidomide after Intensive Chemotherapy in Acute Myeloid Leukemia Patients

INTRODUCTION

Despite the efficacy and outcome of AML patients increases in recent decades, the rate of relapse is still high, especially in the patients who are ineligible for allo-HSCT. How to prevent relapse is still a major therapeutic challenge. Recently, several drugs including Azacitidine (AZA), CC-486, Lenalidomide, androgen, Midostaurin, etc, used as maintenance therapy have shown a better EFS or OS, indicating that maintenance therapy is an important aspect of AML treatment.

Herein, we reported the data of 11 AML patients who were administered AZA combined with Danazol (DNZ) and Thalidomide (THD) as maintenance therapy after intensive chemotherapy (IC). The purpose of this study was to observe the efficacy and safety of this maintenance therapy.

METHODS

Between Feb 2017 and Mar 2021, 11 patients diagnosed with AML were treated at the Baiyun Hospital.

The induction therapy involved daunorubicin (DNR) 60 mg/m²/day on days 1-3, cytarabine (Ara-c) 100 mg/m²/day on days 1-7. If the patient did not achieve CR, salvage therapy was administered. Post-remission, three cycles of consolidation chemotherapy with high-dose Ara-c (3g/m²/q12h d1-3) and two cycles of reduced dose of chemotherapy (DA/HA/EA) were administered.

Patient remained in CR after IC and was treated with 6-8 cycles of AZA combined with DNZ and THD maintenance therapy. AZA subcutaneous injection at 100 mg/day (approximate 50-75 mg/m²/day) d1-7, DNZ 200 mg Bid and THD 100 mg/day po followed by AZA, every four weeks. After completing the 6-8 cycles, patients continued the maintenance therapy with DNZ and THD for at least three years unless relapse or intolerance occurred.

Disease evaluation included bone marrow and blood test until the duration of CR over five years.

RESULTS

Between Feb 2017 and Mar 2021, 11 patients who were enrolled in this study. Baseline patient and disease characteristics are summarized in Table 1.

All 11 patients were treated with DA induction therapy, 10 patients achieved CR, 1 patient achieved remission after salvage therapy. 10 of 11 patients completed all consolidation therapies. 1 patient diagnosed AML with t (8;21) refused to continue chemotherapy because of renal failure after CR, and was directly switched to maintenance therapy. 9 0f 10 patients completed all IC and started on maintenance therapy. 1 AML with t (8;21) patient relapsed after stopping chemotherapy for two months and achieved CR2 by FLAG re-induction therapy refused continued chemotherapy and transplantation, and was directly switched to maintenance therapy.

All patients received a median of 7 (6-12) courses of AZA combined with DNZ and THD maintenance therapy. Treatment was well tolerated and accepted by the patients. Common adverse events included mild neutropenia, thrombocytopenia, and elevated aminotransferase. No patient discontinued the maintenance therapy due to adverse events.

Until June 2022, the median follow-up time was 37 (14-63) months. The RFS at 1-year and 3-years was 100% and 71.1%; the OS at 3-years was 100%, respectively (Figure 1a, 1b). All 11 patients, 3 died and 8 patients were alive with RFS. Of the 3 patients who died, 1 relapsed at 36 months and died due to disease progression at 46 months. The remaining 2 patients, one was diagnosed and died with secondary mixed phenotypic acute leukemia (NOS, T/My), the other died in a road accident. Notably, 2 cases of AML with t (8; 21) (one patient relapsed after IC, another patient developed renal failure) remained in CR by the end of follow-up. The CR duration was 24 and 13 months, respectively. The clinical outcomes of maintenance therapy after IC treatment for 11 patients are summarized in Figure 1c.

Conclusion: AZA combined with DNZ and THD maintenance therapy is safe and effective in AML patients who are ineligible for allo-HSCT.

Keywords: Azacitidine; Danazol; thalidomide; maintenance therapy; AML

Figure 1 Response and long-term outcomes of the entire cohort

Figure 1 legend, a. Relapse-free survival of the 11 patients. b. Overall survival of the 11 patients. c. Swimmer plot of the 11 patients.

No relevant conflicts of interest to declare.