How I treat refractory and relapsed acute myeloid leukemia.

Most patients with acute myeloid leukemia (AML) develop refractory/relapsed (R/R) disease even in the presence of novel and targeted therapies. Given the biological complexity of the disease and differences in frontline treatments, there are therapies approved for only subgroups of R/R AML, and enrollment in clinical trials should be first priority. Allogeneic hematopoietic cell transplantation (HCT) is the only potentially curative strategy for most patients. Therapeutic approaches, including allogeneic HCT, triggered by the presence of measurable residual disease (MRD), have recently evolved to prevent overt hematologic relapse. Salvage therapy with chemotherapy or targeted therapy is frequently administered before HCT to reduce the leukemic burden. Gilteritinib is approved by the Food and Drug Administration and European Medicines Agency for patients with relapsed FLT3 mutated AML, whereas targeted therapy for relapsed IDH1/2 mutated AML has only FDA approval. Patients who are R/R after azacitidine and venetoclax (AZA/VEN) have a dismal outcome. In this setting, even available targeted therapies show unsatisfactory results. Examples of ongoing developments include menin inhibitors, a targeted therapy for patients with mutated NPM1 or KMT2A rearrangements, antibodies targeting the macrophage immune checkpoint CD47, and triple combinations involving AZA/VEN. The latter cause significant myelosuppressive effects, which make it challenging to find the right schedule and dose.

Thol F ，Döhner H ，Ganser A 《-》

Treatment of Relapsed Acute Myeloid Leukemia.

Thol F ，Ganser A 《-》

Allogeneic hematopoietic cell transplantation for acute myeloid leukemia in first complete remission after 5-azacitidine and venetoclax: a multicenter retrospective study.

The combination of hypomethylating agents and venetoclax has revolutionized the therapeutic landscape of acute myeloid leukemia (AML), especially for patients previously deemed unfit for curative-intent treatment. Some of these patients undergo allogeneic hematopoietic cell transplant (alloHCT); yet, there are scarce data regarding transplantation outcomes. We conducted a multicenter nationwide retrospective cohort study, including patients with AML who underwent alloHCT in CR1 after frontline treatment with azacitidine plus venetoclax only (aza-ven group). We collected a historical control group of patients who achieved CR1 after first-line intensive chemotherapy only, followed by alloHCT (intensive group). Patients in the aza-ven group (n = 24) were transplanted between 2019 and 2021. Compared to the intensive group, patients in the aza-ven group were older (median age 71.7 vs. 58.4 years), had higher incidence of therapy-related AML and AML with antecedent hematologic disorder and had more often adverse cytogenetics. They had a higher percentage of allografts from matched-unrelated donors, and reduced intensity conditioning was more commonly used. The estimated 12 months non relapse mortality was 19.1% in the aza-ven group and 11.8% in the intensive group. The estimated 12 months relapse-free survival and overall survival were 58% and 63% in the aza-ven group and 54% and 70% in the intensive group, respectively. The cumulative incidence of acute GVHD at 6 months and of chronic GVHD at 12 months were 58% and 40% in the aza-ven group and 62% and 42% in the intensive group, respectively. Analysis of the aza-ven group revealed that HCT-CI score and ELN risk category were predictive of RFS in both univariate analysis as well as multivariate analysis. Our data suggests that alloHCT for AML patients achieving first CR with aza-ven appears feasible, with short-term post-transplant outcomes similar to those expected after traditional intensive chemotherapy.

Pasvolsky O ，Shimony S ，Ram R ，Shimoni A ，Shargian L ，Avni B ，Wolach O ，Shochat T ，Yerushalmi R ，Amit O ，Raanani P ，Yeshurun M ... -  《-》

Azacitidine-venetoclax versus azacitidine salvage treatment for primary induction failure or first relapsed acute myeloid leukaemia patients.

Petit C ，Saillard C ，Mohty B ，Hicheri Y ，Villetard F ，Maisano V ，Charbonnier A ，Rey J ，D'Incan E ，Rouzaud C ，Gelsi-Boyer V ，Murati A ，Lhoumeau AC ，Ittel A ，Mozziconacci MJ ，Alary AS ，Hospital MA ，Vey N ，Garciaz S ... -  《-》

[Short-term efficacy of venetoclax combined with azacitidine in acute myeloid leukemia: a single-institution experience].

Yu WJ ，Jia JS ，Wang J ，Tang FF ，Gong LZ ，Liu XH ，Zhu XL ，Zhao XS ，Huang XJ ，Jiang H ... -  《-》