The mTOR inhibitor everolimus in combination with azacitidine in patients with relapsed/refractory acute myeloid leukemia: a phase Ib/II study

• DOI: 10.18632/oncotarget.13699
• Publication Date: 2016-11-29T21:53:08Z
• Authors: Peter Tan; Ing Soo Tiong; Shaun Fleming; Giovanna Pomilio; Nik Cummings; Mark Droogleever; Julie McManus; Anthony Schwarer; John Catalano; Sushrut Patil; Sharon Avery; Andrew Spencer; Andrew Wei
• Keywords: Azacitidine; Everolimus; Refractory (planetary science)

Therapeutic options are limited in relapsed/refractory acute myeloid leukemia (AML). We evaluated the maximum tolerated dose (MTD) and preliminary efficacy of mammalian target rapamycin (mTOR) inhibitor, everolimus (days 5-21) combination with azacitidine 75 mg/m2 subcutaneously 1-5 8-9 every 28 days) 40 patients relapsed (n = 27), primary refractory 11) or elderly unfit for intensive chemotherapy 2). MTD was not reached following escalation (2.5, 5 10 mg; n 19) to mg level which expanded 21). Major adverse events (grade > 2) were mostly disease-related: neutropenia (73%), thrombocytopenia (67%), mucositis (24%) febrile (19%). Overall survival (OS) entire cohort 8.5 months, overall response rate (ORR; including CR/CRi/PR/MLFS) 22.5%. Furthermore, a landmark analysis beyond cycle 1 revealed superior OS ORR receiving 2.5 azoles, compared those without azoles (median 12.8 vs. 6.0 P 0.049, 50% 16%, 0.056), potentially due achievement higher blood levels. This study demonstrates that is tolerable, promising clinical activity advanced AML.