The Efficacy and Safety of Decitabine in Combination with ATRA, G-CSF and Low Dose Cytarabine(Dlaag Regimen)in Relapsed/Refractory Acute Myeloid Leukemia Not Suitable for Strong Chemotherapy : A Phase 2, Prospective, Single-Arm, Multicenter Study

Background.

Patients with relapsed or refractory acute myeloid leukemia (R/R AML)who are intolerant of strong regimen chemotherapy have poor responsibility to chemotherapy and clinic remission is lower. The DNMT is depleted to reactivate the silencing tumor suppressor gene to exert anti-tumor effects. Vitro experiments confirmed that ATRA has an anti-leukemia effect on non-M3-AML cell lines. We perform the 2 phase, single-arm, multicenter study of Decitabine in Combination with ATRA, G-CSF and low dose cytarabine(DLAAG Regimen)in R/R AML not suitable for strong chemotherapy (NCT03356080).

Methods.

R/R AML patients aged more than 18 years not suitable for strong chemotherapy were eligible to enroll on this study. The objective was to assess the responses and safety of this therapy. All patients received subcutaneous decitabine injection 0.1-0.2mg/kg on days 1-3 ,8-10,15-17 .ATRA was taken orally at 45mg/m² on day 4-6 and 15mg/m²on days 7-20. Subcutaneous injection cytarabine 15mg/m² every 12 hours on days 1-10 and G-CSF 300ug/d on day 0 until disease remission or absolute neutrophils count ≥ 0.5×109/L were administered. The FLT3 inhibitor, arsenious acid, and the JAK-2 inhibitor, rotectinib, were allowed to be combined.All patients received one or two courses of induction treatments.

Results.

During the period from December 1, 2017 to July 2019, a total of 33 patients were recruited, including 17 women and 16 men. The median age is 64 years (range 46-82). In 33 patients, the overall response rate (ORR = CR + PR) was 36.3%, and the complete response rate (CRR = CR + CRi) was 33.3%. The early treatment-related mortality rate was 6.0%. One died of infection and one died of organ bleeding. Of the 26 patients with karyotype data, 11 received CR. Seven patients (63.6%) in CR showed normal karyotype, 2 patients (18.1%) in CR, and 1 patient (9.0%) in PR showed other moderate karyotypes. One case (9.0%) of the CR group had a poor karyotype. Statistical analysis showed that there was a statistically significant difference between the different karyotype groups (P < 0.05). Only 2 of the 10 FLT3 mutant patients achieved CR (20%). Two patients with abnormal MLL gene did not receive CR.

Conclusions

DLAAG regimen is effective and tolerated in patients with R/R AML who are not suitable for intensive therapy and could be as a bridging therapy regimen followed by HSCT.