**Abstract 2732:** Glasdegib, an oral small molecule inhibitor of the Hedgehog pathway component Smoothened (SMO), was evaluated in combination with low-dose cytarabine (LDAC) or intensive chemotherapy in patients with acute myeloid leukemia (AML). The study aimed to assess the safety and 'on-target' adverse events (AEs) of glasdegib. Safety data from a Phase 1b + Phase 2 multicenter study were pooled, including patients treated with glasdegib 100 mg QD with LDAC (non-intensive treatment) or with cytarabine/daunorubicin on a 7+3 schedule (intensive treatment). The frequency of muscle spasms, alopecia, and dysgeusia, which are 'on-target' AEs, was similar between the two groups. Muscle spasms occurred in 21.3% of the non-intensive group and 23.1% of the intensive group, with few grade 3 events. Alopecia was reported in 90% of the non-intensive group and 20.5% of the intensive group, likely due to the concomitant chemotherapy. Dysgeusia occurred in 24.7% of the non-intensive group and 30.8% of the intensive group. The number of patients requiring dose modifications for on-target AEs was low. The results suggest that glasdegib can be safely combined with standard chemotherapy in AML, with manageable toxicity profiles. **Abstract 285:** Venetoclax, an oral agent targeting the antiapoptotic protein BCL-2, was combined with hypomethylating agents (decitabine or azacitidine) in patients with AML ineligible for intensive chemotherapy. The study aimed to evaluate the safety and efficacy of this combination. Patients received venetoclax at 400 mg daily for 3 days, followed by co-administration with either decitabine or azacitidine. Key grade ≥3 AEs included febrile neutropenia, anemia, pneumonia, thrombocytopenia, and neutropenia. The combination led to high rates of rapid and deep responses, with complete remission (CR/CRi) rates of 70% and 74% for Ven + Aza and Ven + Dec, respectively. The median overall survival was 14.9 months for Ven + Aza and 16.2 months for Ven + Dec. Among patients achieving CR/CRi, 45% achieved minimal residual disease (MRD) negativity. The combination also achieved transfusion independence in 52% of patients who were transfusion dependent at baseline. These results suggest that venetoclax combined with hypomethylating agents may provide a potent therapeutic option for AML**Abstract 2732:** Glasdegib, an oral small molecule inhibitor of the Hedgehog pathway component Smoothened (SMO), was evaluated in combination with low-dose cytarabine (LDAC) or intensive chemotherapy in patients with acute myeloid leukemia (AML). The study aimed to assess the safety and 'on-target' adverse events (AEs) of glasdegib. Safety data from a Phase 1b + Phase 2 multicenter study were pooled, including patients treated with glasdegib 100 mg QD with LDAC (non-intensive treatment) or with cytarabine/daunorubicin on a 7+3 schedule (intensive treatment). The frequency of muscle spasms, alopecia, and dysgeusia, which are 'on-target' AEs, was similar between the two groups. Muscle spasms occurred in 21.3% of the non-intensive group and 23.1% of the intensive group, with few grade 3 events. Alopecia was reported in 90% of the non-intensive group and 20.5% of the intensive group, likely due to the concomitant chemotherapy. Dysgeusia occurred in 24.7% of the non-intensive group and 30.8% of the intensive group. The number of patients requiring dose modifications for on-target AEs was low. The results suggest that glasdegib can be safely combined with standard chemotherapy in AML, with manageable toxicity profiles. **Abstract 285:** Venetoclax, an oral agent targeting the antiapoptotic protein BCL-2, was combined with hypomethylating agents (decitabine or azacitidine) in patients with AML ineligible for intensive chemotherapy. The study aimed to evaluate the safety and efficacy of this combination. Patients received venetoclax at 400 mg daily for 3 days, followed by co-administration with either decitabine or azacitidine. Key grade ≥3 AEs included febrile neutropenia, anemia, pneumonia, thrombocytopenia, and neutropenia. The combination led to high rates of rapid and deep responses, with complete remission (CR/CRi) rates of 70% and 74% for Ven + Aza and Ven + Dec, respectively. The median overall survival was 14.9 months for Ven + Aza and 16.2 months for Ven + Dec. Among patients achieving CR/CRi, 45% achieved minimal residual disease (MRD) negativity. The combination also achieved transfusion independence in 52% of patients who were transfusion dependent at baseline. These results suggest that venetoclax combined with hypomethylating agents may provide a potent therapeutic option for AML