Acute myeloid leukemia (AML) treatment has seen the addition of novel agents like glasdegib and venetoclax, which have shown improved outcomes. Glasdegib, an oral inhibitor of the Hedgehog pathway, was studied in combination with chemotherapy in AML patients. The study found that glasdegib added to low-dose cytarabine (LDAC) or intensive chemotherapy (7+3 regimen) improved overall survival and was generally well tolerated. 'On-target' adverse events included muscle spasms, alopecia, and dysgeusia, which were mostly mild and did not lead to significant treatment discontinuation. The combination of glasdegib with standard chemotherapy had a manageable safety profile, and results were consistent with previously reported safety outcomes for glasdegib as monotherapy. Venetoclax, an inhibitor of BCL-2, was studied in combination with hypomethylating agents (HMA) in patients ineligible for intensive chemotherapy. The combination showed high rates of rapid, deep, and durable responses, with many patients achieving complete remission (CR/CRi) and transfusion independence. Key toxicities included febrile neutropenia, anemia, and thrombocytopenia, which were similar to those seen with standard induction chemotherapy. Venetoclax in combination with HMA provided a potent therapeutic option for patients with AML not eligible for intensive chemotherapy. Another study explored the synergistic anti-leukemic activity of quizartinib (FLT3 inhibitor) and milademetan (MDM2 inhibitor) in FLT3-ITD mutant/p53 wild-type AML models. The combination showed significant synergistic pro-apoptotic effects, leading to enhanced cell death and tumor growth inhibition in preclinical models. This combination is being evaluated in a phase I clinical trial for patients with FLT3-ITD mutant AML. These studies highlight the importance of understanding the safety and efficacy of novel agents in combination with standard chemotherapy for AML patients. Advanced practitioners should be aware of these treatment options and their associated side effects to provide optimal care. As new agents continue to be developed and tested, it is crucial for APs to stay informed and adapt treatment strategies accordingly.Acute myeloid leukemia (AML) treatment has seen the addition of novel agents like glasdegib and venetoclax, which have shown improved outcomes. Glasdegib, an oral inhibitor of the Hedgehog pathway, was studied in combination with chemotherapy in AML patients. The study found that glasdegib added to low-dose cytarabine (LDAC) or intensive chemotherapy (7+3 regimen) improved overall survival and was generally well tolerated. 'On-target' adverse events included muscle spasms, alopecia, and dysgeusia, which were mostly mild and did not lead to significant treatment discontinuation. The combination of glasdegib with standard chemotherapy had a manageable safety profile, and results were consistent with previously reported safety outcomes for glasdegib as monotherapy. Venetoclax, an inhibitor of BCL-2, was studied in combination with hypomethylating agents (HMA) in patients ineligible for intensive chemotherapy. The combination showed high rates of rapid, deep, and durable responses, with many patients achieving complete remission (CR/CRi) and transfusion independence. Key toxicities included febrile neutropenia, anemia, and thrombocytopenia, which were similar to those seen with standard induction chemotherapy. Venetoclax in combination with HMA provided a potent therapeutic option for patients with AML not eligible for intensive chemotherapy. Another study explored the synergistic anti-leukemic activity of quizartinib (FLT3 inhibitor) and milademetan (MDM2 inhibitor) in FLT3-ITD mutant/p53 wild-type AML models. The combination showed significant synergistic pro-apoptotic effects, leading to enhanced cell death and tumor growth inhibition in preclinical models. This combination is being evaluated in a phase I clinical trial for patients with FLT3-ITD mutant AML. These studies highlight the importance of understanding the safety and efficacy of novel agents in combination with standard chemotherapy for AML patients. Advanced practitioners should be aware of these treatment options and their associated side effects to provide optimal care. As new agents continue to be developed and tested, it is crucial for APs to stay informed and adapt treatment strategies accordingly.