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
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-group | MRD-ve | Relapse free |
---|---|---|
Total | 20/25 (80%) | 21/25 (84%) |
MRD-ve at CR1 | 20 | 18/20 (90%) |
MRD+ve at CR1 | 5 | 3/5 (60%) |
<60y | 14/15 (93%) | 14/15 (93%) |
≥60y | 6/10 (60%) | 7/10 (70%) |
WBC >100,000/µL | 4/4 (100%) | 4/4 (100%) |
FLT3/NPM1/DNMT3A+ve | 5/5 (100%) | 5/5 (100%) |
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Abstract Disclosures
2022 ASCO Annual Meeting
First Author: Eunice S. Wang
2019 ASCO Annual Meeting
First Author: Richard M. Stone
2024 ASCO Annual Meeting
First Author: Ahmed Bilal Khalid
2018 ASCO Annual Meeting
First Author: Adolfo Fuentes