IMPACT OF MINIMAL RESIDUAL DISEASE AND COMPLETE REMISSION (CR)/CR WITH PARTIAL HEMATOLOGIC RECOVERY ON SURVIVAL AFTER GILTERITINIB THERAPY IN PATIENTS WITH FLT3-MUTATED RELAPSED/REFRACTORY AML
Author(s): ,
Mark Levis
Affiliations:
Sidney Kimmel Comprehensive Cancer Center,Johns Hopkins University,Baltimore,United States
,
Alexander Perl
Affiliations:
Abramson Cancer Center,University of Pennsylvania,Philadelphia,United States
,
Jessica Altman
Affiliations:
Robert H. Lurie Comprehensive Cancer Center,Northwestern University Feinberg School of Medicine,Chicago,United States
,
Jorge Cortes
Affiliations:
Department of Leukemia,University of Texas M.D. Anderson Cancer Center,Houston,United States
,
Catherine Smith
Affiliations:
University of California,San Francisco,United States
,
Maria Baer
Affiliations:
University of Maryland Greenebam Comprehensive Cancer Center,Baltimore,United States
,
David Claxton
Affiliations:
Penn State Milton S. Hershey Medical Center,Hershey,United States
,
Joseph Jurcic
Affiliations:
Columbia University Medical Center,New York,United States
,
Ellen Ritchie
Affiliations:
Weill Cornell Medical College,New York,United States
,
Stephen Strickland
Affiliations:
Vanderbilt-Ingram Cancer Center,Nashville,United States
,
Raoul Tibes
Affiliations:
Laura & Isaac Perlmutter Cancer Center,NYU Langone Health and NYU School of Medicine,New York,United States
,
Jason Hill
Affiliations:
Astellas Pharma Global Development,Northbrook,United States
,
Matt Rosales
Affiliations:
Astellas Pharma Global Development,Northbrook,United States
Erkut Bahceci
Affiliations:
Astellas Pharma Global Development,Northbrook,United States
EHA Library. Levis M. Jun 15, 2019; 266641; PS1024
Dr. Mark Levis
Dr. Mark Levis
Contributions
Abstract

Abstract: PS1024

Type: Poster Presentation

Presentation during EHA24: On Saturday, June 15, 2019 from 17:30 - 19:00

Location: Poster area

Background
Gilteritinib, a highly selective FLT3 inhibitor, demonstrated strong antileukemic activity at doses ≥80 mg/day in patients with FLT3-mutated (FLT3mut+) relapsed/refractory (R/R) AML enrolled in the CHRYSALIS phase 1/2 study (NCT02014558). 

Aims
We analyzed the impact of minimal residual disease (MRD) and achievement of complete remission/complete remission with partial hematologic recovery (CR/CRh) on overall survival (OS) in patients with FLT3mut+ R/R AML from the CHRYSALIS study.

Methods
Minimal residual disease was assessed by next-generation sequencing (NGS) using an Illumina® sequencing platform that quantified FLT3-ITD and total FLT3 alleles in FLT3-ITDmut+ patients who had bone marrow samples available at baseline and at ≥1 post-baseline time point. The ITD variant allele frequency (VAF) was the FLT3-ITD to total FLT3 ratio. An ITD VAF ≤10−4 defined MRD-negative (MRD−) status. For FLT3 VAF, a capture-based NGS assay that included all FLT3 exons was used. Treatment response was evaluated according to the CR/CRh rate, where CRh was defined as absolute neutrophil count >0.5 × 109/L and platelet count >50 × 109/L. 

Results
Of the 108 FLT3-ITDmut+ patients analyzed for MRD, 95 had received ≥80 mg/day gilteritinib, which was shown to induce maximum FLT3 inhibition and antileukemic response. Of the 95 patients, 82 were MRD-positive (MRD+) and 13 achieved MRD− status at any post-baseline time point; 49 of 95 patients had a best overall response (BOR) of composite complete remission (CRc; ie, CR plus CR with incomplete hematologic or platelet recovery) and 11 were MRD−. No patient who received <80 mg/day gilteritinib achieved MRD− status. Of the 46 patients who did not achieve CRc, two were MRD−. Patients who had achieved CRc and were MRD− (n=11) had longer median OS (168.7 weeks) than those who had achieved CRc and were MRD+ (n=38; 36.1 weeks; P=.004) (Figure 1). Excluding patients with an OS duration less than the median time to reach MRD− status, MRD− patients (n=12) had a median OS of 131.4 weeks (95% CI: 35.1, not reached) compared with MRD+ patients (n=38) who had a median OS of 47.3 weeks. Of the 95 patients who received ≥80 mg/day gilteritinib in the MRD analysis, 24 had a best overall response of CR/CRh. Of the 24 patients with CR/CRh, 10 (41.67%) were MRD−. Of the 71 patients without CR/CRh, three (4.2%) were MRD−. Patients who received 120 mg/day gilteritinib were previously shown to have longer survival than patients in other dose cohorts. Of the 56 patients who received 120 mg/day gilteritinib, 13 achieved a BOR of CR/CRh. Patients who achieved CR/CRh had a median OS of 70.6 weeks and a 52-week survival probability of 66.7%, whereas those who did not achieve CR/CRh had a median OS of 32.4 weeks and a 52-week survival probability of 20.2% (Figure 2).

Conclusion
Single-agent therapy with gilteritinib induced deep molecular responses in heavily pretreated patients with FLT3-ITDmut+ R/R AML. Our results suggest a potential association between MRD negativity and longer survival in these patients; achievement of CR/CRh appears to be associated with a higher rate of MRD negativity and longer OS.

Session topic: 4. Acute myeloid leukemia - Clinical

Keyword(s): Acute myeloid leukemia, Flt3-ITD, Molecular response

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