616. Acute Myeloid Leukemia: Novel Therapy, excluding Transplantation: Novel combination therapies in treatment of newly diagnosed AML

Keith W. Pratz, Mohamad Cherry, Jessica K. Altman, et al.

Authors Conclusion from the Abstract: Gilteritinib plus induction and consolidation chemotherapy is well tolerated in patients with newly diagnosed AML. Favorable antileukemic responses were observed in FLT3mut+ patients regardless of anthracycline type or gilteritinib administration schedule, with a mutational clearance rate of 70.0%. Based on these results, randomized clinical trials of induction and consolidation chemotherapy plus gilteritinib vs midostaurin in FLT3mut+AML patients have been initiated.

Tapan M. Kadia, Gautam Borthakur, Naveen Pemmaraju, et al.

Authors Conclusion from the Abstract: CLAD/LDAC plus venetoclax alternating with AZA plus venetoclax is an effective, lower-intensity regimen that is well tolerated among older patients with newly diagnosed AML, producing high rates of durable MRD negative remission and meaningful blood count recovery. With approximately 1-year follow-up, the rates of overall and relapse-free survival are encouraging in this cohort of older AML patients. Further study of this backbone in combination approaches is warranted.

Musa Yilmaz, Hagop M. Kantarjian, Muharrem Muftuoglu, et al.

Authors Conclusion from the Abstract: DAC10 + venetoclax + quiz is highly active in R/R FLT3-ITD mut AML pts, with CRc rates of 90% and projected 6-month OS of 86%. CYTOF profiling may predict for response based on pre- and on-therapy apoptotic and signaling pathway profiles enabling potential optimal selection of future combinatorial or sequential approaches. Accrual to the triplet continues and updated clinical and correlative data will be presented.

Eunice S. Wang, Pau Montesinos, Mark D. Minden, et al.

Authors Conclusion from the Abstract: The study is ongoing, and no new safety signals associated with gilteritinib 120 mg daily plus AZA have been observed thus far in the study. Mature remission data from the Safety Cohort of gilteritinib 80-120 mg plus AZA shows a CRc rate of 67%. Patients with ND FLT3mut+ AML considered unfit for intensive chemotherapy continue to be randomized 2:1 to receive gilteritinib 120 mg/d plus AZA vs AZA alone for upfront treatment.

Tapan M. Kadia, Gautam Borthakur, Koichi Takahashi, et al.

Authors Conclusion from the Abstract: CPX-351 plus 7 days of Ven is tolerable, with acceptable toxicities in patients with R/R AML. Within this high risk AML cohort, CPX + Ven demonstrated encouraging activity, particularly in those who had not received prior Ven. Almost all responders were able to move on to SCT. The study continues to enroll relapsed and frontline cohorts.

Musa Yilmaz, Mansour Alfayez, Tapan M. Kadia, et al.

Authors Conclusion from the Abstract: The CRc rates and median OS dropped with sequential FLT3i exposure, from induction to post-induction salvage (cohort 1) and sequentially in subsequent salvages (cohort 2). FLT3i combinations demonstrated improved CRc rates and improved OS compared with single agent FLT3i’s in all similar FLT3i exposure settings. Achievement of MRD negativity by FLT3-PCR improved OS in R/R setting. These data provide benchmark expectations in the “post-midostaurin” and now “post-gilteritinib” era for clinical trials evaluating combinations of FLT3i’s with chemotherapy, hypomethylating agents, venetoclax, and triplets of hypomethylating agents with venetoclax and FLT3i’s in R/R FLT3-AML, a majority of whom will have received one or more prior FLT3 TKI therapies.