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Attend this session at the
2019 ASCO Annual Meeting!


Session: Hematologic Malignancies—Leukemia, Myelodysplastic Syndromes, and Allotransplant

Type: Oral Abstract Session

Time: Saturday June 1, 3:00 PM to 6:00 PM

Location: E451

Effect of gilteritinib on survival in patients with FLT3-mutated (FLT3mut+) relapsed/refractory (R/R) AML who have common AML co-mutations or a high FLT3-ITD allelic ratio.

Sub-category:
Acute Leukemia

Category:
Hematologic Malignancies—Leukemia, Myelodysplastic Syndromes, and Allotransplant

Meeting:
2019 ASCO Annual Meeting

Abstract No:
7000

Citation:
J Clin Oncol 37, 2019 (suppl; abstr 7000)

Author(s): Mark J. Levis, Alexander E. Perl, Giovanni Martinelli, Jorge E. Cortes, Andreas Neubauer, Ellin Berman, Pau Montesinos, Maria R. Baer, Richard A. Larson, Wen-Chien Chou, Hisayuki Yokoyama, Christian Recher, Sung-Soo Yoon, Jason E Hill, Matt Rosales, Charles Liu, Erkut Bahceci; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD; Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA; Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy; The University of Texas MD Anderson Cancer Center, Houston, TX; Universitätsklinikum Giessen und Marburg GmbH, Marburg, Germany; Memorial Sloan Kettering Cancer Center, New York, NY; Hospital Universitari i Politècnic La Fe, Valencia & CIBERONC, Instituto Carlos III, Madrid, Spain; University of Maryland Greenebaum Comprehensive Cancer Center (UMGCCC), Baltimore, MD; The University of Chicago, Chicago, IL; National Taiwan University, Taipei City, Taiwan; Sendai Medical Center, National Hospital Organization, Sendai, Japan; Institut Universitaire du Cancer Toulouse–Oncopole, Cedex, France; Seoul National University, Seoul, South Korea; Astellas Pharma US, Inc., Northbrook, IL

Abstract Disclosures

Abstract:

Background: The FLT3 inhibitor, gilteritinib, showed superior response and overall survival (OS) compared with salvage chemotherapy (SC) in patients (pts) with FLT3mut+ R/R AML in the phase 3 ADMIRAL study. We analyzed the impact of baseline co-mutations and FLT3-ITD allelic ratio (AR) on response and OS. Methods: A total of 37 recurrently mutated genes in AML (Archer Core Myeloid Panel) were analyzed by next-generation sequencing; the cutoff for co-mutation positivity (co-mut+) was ≥0.027. Baseline FLT3-ITD AR (FLT3-ITD to FLT3 wild-type DNA) was measured by the LeukoStrat CDx FLT3 Mutation Assay. The median FLT3-ITD AR value of 0.77 was used to define high (≥0.77) vs low (<0.77) FLT3-ITD AR. Results: Analysis of 361 FLT3mut+ pts identified four major co-mutation cohorts, each with ≥10% of pts: NPM1 (n=173; 47.9%), DNMT3A (n=115; 31.9%), DNMT3A/NPM1 (n=86; 23.8%), and WT1 (n=65; 18.0%). In addition, seven pts (1.9%) had all three co-mutations (ie, NPM1, DNMT3A, and WT1). The gilteritinib arm had superior response rates and OS across all four major co-mutation cohorts, with the greatest survival benefit in pts with DNMT3A/NPM1 co-mut+ (Table). In FLT3-ITD AR analyses (n=335), gilteritinib conferred longer OS than SC in pts with a high or low FLT3-ITD AR (gilteritinib: high FLT3-ITD AR, 7.1 mos vs low FLT3-ITD AR, 10.6 mos; SC: high FLT3-ITD AR, 4.3 mos vs low FLT3-ITD AR, 6.9 mos). In both arms, OS was longer in the low FLT3-ITD AR cohort than the high FLT3-ITD AR cohort but the difference in the gilteritinib arm was not statistically significant (gilteritinib: HR=1.341, P=0.0712; SC: HR=2.01, P=0.0021). Conclusions: The ADMIRAL trial shows that the clinical benefit of gilteritinib in FLT3mut+ R/R AML is maintained regardless of NPM1, DNMT3A, DNMT3A/NPM1, or WT1 co-mut+ or high FLT3-ITD AR. Clinical trial information: NCT02421939

PatientsCR/CRh (%)
Median OS (mos)
GilteritinibSCGilteritinibSCHRP-Value
ITT population (n=371)34.015.39.35.60.6370.0007
Co-mut+ cohorts
NPM1 (n=173)32.212.18.35.10.419<0.0001
DNMT3A (n=115)37.312.59.15.50.5040.0031
DNMT3A/NPM1 (n=86)40.09.710.85.00.252<0.0001
WT1 (n=65)35.65.09.13.40.3090.0001

 
Other Abstracts in this Sub-Category:

 

1. A randomized phase II trial of CX-01 with standard therapy in elderly patients with acute myeloid leukemia (AML).

Meeting: 2019 ASCO Annual Meeting Abstract No: 7001 First Author: Tibor Kovacsovics
Category: Hematologic Malignancies—Leukemia, Myelodysplastic Syndromes, and Allotransplant - Acute Leukemia

 

2. Association of smoking with poor risk ELN 2017, cytogenetics/molecular profile, and survival outcomes in acute myeloid leukemia.

Meeting: 2019 ASCO Annual Meeting Abstract No: 7002 First Author: Mansour Alfayez
Category: Hematologic Malignancies—Leukemia, Myelodysplastic Syndromes, and Allotransplant - Acute Leukemia

 

3. End of phase I results of ZUMA-3, a phase 1/2 study of KTE-X19, anti-CD19 chimeric antigen receptor (CAR) T cell therapy, in adult patients (pts) with relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL).

Meeting: 2019 ASCO Annual Meeting Abstract No: 7006 First Author: Bijal D. Shah
Category: Hematologic Malignancies—Leukemia, Myelodysplastic Syndromes, and Allotransplant - Acute Leukemia

 

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