Effect of cytarabine/anthracycline/crenolanib induction on minimal residual disease (MRD) in newly diagnosed FLT3 mutant AML.

Authors

null

Richard M. Stone

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA

Richard M. Stone , Robert Collins , Martin S. Tallman , Roland B. Walter , Chatchada Karanes , Prapti Arvind Patel , Madhuri Vusirikala , Catherine Callaghan Coombs , Gretchen Olson , Vinay Kumar Jain , Eunice S. Wang

Organizations

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, The University of Texas Southwestern Medical Center, Dallas, TX, Department of Medicine, Leukemia Service, Memorial Sloan Kettering Cancer Center, New York, NY, Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, Department of Hematology and Hematopietic Cell Transplantation, City of Hope, Duarte, CA, Memorial Sloan-Kettering Cancer Center, New York, NY, Roswell Park Cancer Institute, Buffalo, NY, AROG Pharmaceuticals, Inc., Dallas, TX, Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY

Research Funding

Pharmaceutical/Biotech Company

Background: Baseline characteristics such as age >60, WBC>100,000/µL and FLT3/NPM1/DNMT3A+ve are known to be associated with a poor prognosis in AML. Ivey et al. (NEJM 2016) reported that FLT3-ITD+ve patients (pts) who were MRD+ve after 2 cycles of induction chemotherapy were more likely to relapse as compared to those who became MRD-ve (92% vs 35%). Eradication of FLT3+veclones may lead to reduced relapse rates. Crenolanib is a type I FLT3 TKI, which inhibits both FLT3-ITD and TKD mutations. We here report that a single induction cycle of cytarabine/anthracycline/crenolanib leads to MRD negativity by multiparameter flow cytometry (MPF), and low rate of early relapse in pts with newly diagnosed FLT3+veAML. Methods: This abstract includes 29 consecutively treated, newly diagnosed, FLT3+ve AML pts, who achieved CR1 after one course of cytarabine/anthracycline/crenolanib. Pts received 7+3 induction with cytarabine 100 mg/m2/d for 7d and either daunorubicin (<60 y: 90 mg/m2; ≥60 y: 60 mg/m2) or idarubicin 12 mg/m2 for 3d. Crenolanib (100 mg TID) was started on day 9 until 72 h prior to next chemotherapy. Results: 29 pts (15M, 14F), median age 55y (10pts ≥60y) are included. MRD at time of count recovery was assessed by MPF in 25/29 pts. 20/25 (80%) became MRD–ve. With a median follow up of 7mth, 4/25 pts have relapsed (2/5 MRD+ve, 2/20 MRD-ve).Age ≥60 was a risk factor for MRD+ve and relapse. All 4 pts with WBC>100K as well as 5 pts with FLT3/NPM1/DNMT3A+ve AML became MRD-ve after one induction cycle and none have relapsed. Conclusions: These data suggest, in the context of an ongoing trial (NCT02283177), crenolanib in combination with standard induction is associated with a high rate of achieving an MRD negative state by MPF and a low rate of relapse in previously untreated adults with mutant FLT3. Longer follow-up and comparison of MRD data with similar pts treated with standard chemo alone will be necessary to reach more definitive conclusions. Clinical trial information: NCT02283177

Sub-groupMRD-veRelapse free
Total20/25 (80%)21/25 (84%)
MRD-ve at CR12018/20 (90%)
MRD+ve at CR153/5 (60%)
<60y14/15 (93%)14/15 (93%)
≥60y6/10 (60%)7/10 (70%)
WBC >100,000/µL4/4 (100%)4/4 (100%)
FLT3/NPM1/DNMT3A+ve5/5 (100%)5/5 (100%)

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Abstract Details

Meeting

2017 ASCO Annual Meeting

Session Type

Poster Discussion Session

Session Title

Hematologic Malignancies—Leukemia, Myelodysplastic Syndromes, and Allotransplant

Track

Hematologic Malignancies—Leukemia, Myelodysplastic Syndromes, and Allotransplant

Sub Track

Acute Leukemia

Clinical Trial Registration Number

NCT02283177

Citation

J Clin Oncol 35, 2017 (suppl; abstr 7016)

DOI

10.1200/JCO.2017.35.15_suppl.7016

Abstract #

7016

Poster Bd #

216

Abstract Disclosures