Safety of Gemtuzumab Ozogamicin with Cytarabine, Daunorubicin, and Midostaurin Induction in FLT3-Mutated AML Open Access

• The addition of GO to standard of care cytarabine, anthracycline, and midostaurin induction was well-tolerated in ND, FLT3-mutated AML.

• The maximum tolerated dose included two doses of GO 3mg/m² on days 1 and 4.

This phase I study investigated the addition of gemtuzumab ozogamicin (GO) to intensive chemotherapy with cytarabine, daunorubicin, and midostaurin in 21 patients with newly diagnosed, FLT3-mutated acute myeloid leukemia. Four dose levels of GO were evaluated. The use of GO was tolerable since all dose limiting toxicities were similar to those seen in standard of care treatment. After induction, the median time to platelet recovery was 26 days, and the median time to ANC recovery was 27 days. The maximum tolerated dose was cytarabine 100mg/m² on days 1-7, midostaurin 50 mg bid on days 8-21, daunorubicin 60mg/m² on days 1-3, and gemtuzumab ozogamicin 3mg/m² on days 1 and 4. For the 18 patients who were evaluable for response after induction therapy, 16 (76%) patients achieved a composite complete response (CR+CRi) and 2 (10%) had stable disease. Of the 14 patients who proceeded to consolidation, 5 discontinued study for transplant, 1 for disease progression, and 1 for physician discretion. Seven patients completed consolidation therapy, all of whom achieved a complete response (CR). In total, 13 of the 21 patients received a hematopoietic stem cell transplant (62%). Our results show that GO can safely be combined with intensive chemotherapy with midostaurin in newly diagnosed acute myeloid leukemia. ClinicalTrials.gov: # NCT03900949.