616. Acute Myeloid Leukemia: Novel Therapy, excluding Transplantation: Novel promising therapies for relapsed/refractory AML

Hartmut Döhner, Andrew H Wei, Pau Montesinos, et al.

Authors Conclusion from the Abstract: An escalated 21-day CC-486 dosing regimen was well tolerated and resulted in restoration of remission in approximately one-fourth of patients. Hematologic adverse events first reported during escalated dosing in both treatment arms may be due in part to disease relapse. A 21-day CC-486 dosing schedule could be considered for patients who experience AML relapse with ≤ 15% blasts.

Stephane De Botton, Thomas Cluzeau, Carlos Enrique Vigil, et al.

Authors Conclusion from the Abstract: SY-1425 + aza was generally well-tolerated without evidence of increased toxicity of the combination relative to either as a single agent. Importantly, rates of myelosuppression were comparable to single-agent aza in this population. There was evidence of clinical activity with a high CR rate and rapid time to initial response, with evidence of clinical benefit associated with TI in a majority of RARA+ ND unfit AML pts. Use of the novel blood-based biomarker test to predict sensitivity to SY-1425 in AML pts was supported by clinical outcomes, with higher response rates and a more rapid onset in RARA+ vs RARA- pts, whose responses were consistent with single-agent aza. SY-1425 + aza shows potential as a novel targeted regimen for the treatment of RARA+ ND unfit AML and warrants further development in this genomically defined subset of AML pts, as well as other related RARA+ pt populations. Updated data, including mature duration of response and survival, will be presented.

Benjamin J. Huang, Xinyue Wang, Max Harris, et al.

Authors Conclusion from the Abstract: Taken together, our data support the hypothesis that BET inhibitor and MEK inhibitor combination may be a particularly effective therapeutic approach in AML. Additional preclinical testing in patient derived xenograft models is underway.

Eytan M. Stein, Stephane De Botton, Thomas Cluzeau, et al.

Authors Conclusion from the Abstract: SY-1425 in combination with aza was generally well-tolerated with clinical responses observed in this heavily pretreated relapsed/refractory AML population. The early OS estimate is encouraging, especially given the prevalence of HMA +/- venetoclax prior treatment in the study population. SY-1425 in combination with aza shows potential as a novel regimen for the treatment of RARA+ R/R AML.

Eunice S. Wang, Jessica K. Altman, Kristen M. Pettit, et al.

Authors Conclusion from the Abstract: The early biologic activity of KO-539 in relapsed AML is encouraging, and its unique PK characteristics may be advantageous for clinical benefit. In addition to the above, any updated safety, PK, and efficacy data will be presented at the time of the conference.

Inge Van Der Werf, Phoebe Mondala, Raymond Diep, et al.

Authors Conclusion from the Abstract: Cumulatively, our data indicate that spliceosome modulation via 17S-FD-895-mediated targeting of SF3B1 constitutes a novel potential therapeutic strategy for pediatric patients with AML.