Optimizing outcomes in secondary AML

Acute myeloid leukemia (AML) secondary to antecedent hematologic disorder or prior therapeutics for cancer represent a diverse group of leu ke mias often asso ci ated with infe rior out comes. Conventional ther apy with cytarabine -based che mo-ther apy has been the main stay of care for the past 30 years with dis ap point ing over all out comes. Novel ther a pies, includ-ing liposomal cytarabine/daunorubicin, and venetoclax-based therapies have emerged as options in recent years based on studies showing improvement in outcomes over standard-of-care therapies. Despite these advances, mutations in TP53 are asso ci ated with infe rior response to both ther a pies and rep re sent an area of unmet clin i cal need. Novel strat e gies with immune -targeted ther a pies such as CD47 mono clo nal antibodies appear active in early -phase stud ies, but ran dom ized stud ies have yet to report out comes lead ing to approval. Allogeneic trans plant remains the only known cura tive ther apy for many of these cases. Nonetheless, pretransplant high -risk molec u lar fea tures of sec ond ary AML are asso ci ated with infe rior out come despite trans plan ta tion. An opti mal approach to sec ond ary AML is yet to be deter mined.

Automated summary

Acute myeloid leukemia (AML) secondary to antecedent hematologic disorder or prior therapeutics for cancer is a challenging type of leukemia with inferior outcomes. While conventional therapy with cytarabine-based chemotherapy has been the mainstay of care for the past 30 years, recent studies have shown that novel therapies, such as liposomal cytarabine/daunorubicin and venetoclax-based therapies, may lead to improved outcomes. However, mutations in TP53 remain a challenge and there is a need for immune-targeted therapies. Allogeneic transplant is currently the only known curative therapy, but high-risk molecular features of secondary AML are associated with inferior outcomes even after transplant. The optimal approach to secondary AML is yet to be determined.