5‐Azacytidine treatment for relapsed or refractory acute myeloid leukemia after intensive chemotherapy

Abstract

Despite progress in the understanding of leukemia pathophysiology, the treatment of acute myeloid leukemia (AML) remains challenging. In patients with refractory or relapsed (R=R) AML, the prognosis is still poor and this group is targeted for new drug development. We reviewed the outcome of 47 patients, with R=R AML after at least one course of intensive chemotherapy, treated with 5-azacytidine in three different French institutions. The overall response rate was 38% including complete remission in 21%, partial remission in 11%, and hematological improvement in 6% of cases. Median time to relapse was 6 (range, 1-39) months. Median overall survival was 9 months (not reached by responders vs. 4.5 months for nonresponders patients, P 5 0.0001). Univariate analysis identified the absence of peripheral blood blasts and <20% bone marrow blasts as prognostic factors for both overall response and survival, but not age, ECOG=PS, type of AML, cytogenetic, status of the disease, number of previous lines of therapy, previous hematological stem cell transplantation, or white blood cells count. Bone marrow blasts percentage <20% was the only independent prognostic factor identified by multivariate analysis for overall response (P 5 0.0013) and survival (P 5 0.0324). Six patients in remission could proceed to an allogenic hematological stem cell transplantation. The drug-related grade 3=4 adverse events were hematopoietic toxicities (38%) and infection (32%). In conclusion, this study suggests that a salvage therapy with 5-azacytidine is an interesting option for patients with R=R AML after intensive chemotherapy. Prospective randomized studies are needed to demonstrate a superiority of this approach over others strategies. Am. J. Hematol. 88:601-605,

Outcomes of allogeneic stem cell transplantation among patients with acute myeloid leukemia presenting active disease: Experience of a single European Comprehensive Cancer Center

“…The overall response rate was higher (38%) than in our cohort (21.7%) and the median OS (9 months) was also slightly higher than in our study (8 months). 29 However, despite the relatively inferior results compared to the French cohort using 5-azacytidine, our cohort provided a high number of patients (61 versus 47) and a similar OS to the 5-azacytidine study. Of note, randomized clinical trials are warranted in order to compare the real effectiveness of both approaches in relapsed/refractory AML patients.…”

Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel

“…122,[219][220][221][222][223][224][225][226] Enrollment in a clinical trial should therefore be the priority for such patients whenever possible. Table 8 provides recommendations for salvage regimens in patients considered fit for intensive therapy.…”

“…235 In patients not fit for intensive salvage chemotherapy, effective treatment options are lacking. Azacitidine and decitabine induce CR rates of 16% to 21% and median survival times of 6 to 9 months in older patients with relapsed/refractory AML [223][224][225] ; median postrelapse survival after therapy with LDAC is 5 to 6 months. 226 For patients in second or third relapse, various therapeutic options are associated with CR rates of ;20% and median OS outcomes of ;3 months, 221 stressing the need for enrollment into clinical trials.…”

Extended dosing with CC‐486 (oral azacitidine) in patients with myeloid malignancies

“…These studies show azacitidine reduces cytopenias in select lower‐risk MDS and prolongs overall survival (OS) in higher‐risk MDS and AML,5, 6, 7, 16 may be effective maintenance therapy after induction chemotherapy (IC) or allogeneic hematopoietic stem cell transplant (alloHSCT),17, 18, 19, 20 and can induce responses in patients with relapsed/refractory disease 12, 21. Importantly, the study of azacitidine has revealed nuances of treatment with DNMTi therapy not seen with the use of traditional chemotherapy.…”