2017 ASCO Annual Meeting!
Session: Hematologic Malignancies—Leukemia, Myelodysplastic Syndromes, and Allotransplant
Type: Oral Abstract Session
Time: Tuesday June 6, 9:45 AM to 12:45 PM
Distinct patterns of somatic mutation clearance and association with clinical outcome in patients with AML.
Hematologic Malignancies—Leukemia, Myelodysplastic Syndromes, and Allotransplant
2017 ASCO Annual Meeting
J Clin Oncol 35, 2017 (suppl; abstr 7005)
Author(s): Koichi Takahashi, Feng Wang, Keyur Patel, Carlos E. Bueso-Ramos, Ghayas C. Issa, Xingzhi Song, Jianhua Zhang, Samantha Tippen, Latasha Little, Curtis Gumbs, Farhad Ravandi, Tapan M. Kadia, Naval Guastad Daver, Courtney Denton Dinardo, Marina Konopleva, Michael Andreeff, Jorge E. Cortes, Elias Jabbour, Andrew Futreal, Hagop M. Kantarjian; The University of Texas MD Anderson Cancer Center, Houston, TX; The University of Texas MD Anderson Cancer Center, Department of Leukemia, Houston, TX; The University of Texas MD Anderson Cancer Center, Department of Hematopathology, Houston, TX; Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX
Background: Persistence of somatic mutations at the time of complete remission (CR) was associated with poor outcome in patients (pts) with AML. Methods: We studied 95 pts with AML who were treated with frontline induction and subsequently achieved CR. We sequenced pre-treatment and CR bone marrow samples by targeted capture sequencing of 295 genes (median 280x coverage). We defined 3 levels of mutation clearance (MC) based on variant allele frequency (VAF): MC2.5, persistent mutation with VAF<2.5%; MC1.0, persistent mutation with VAF<1%; and complete mutation clearance (CMC). Results: In the pre-treatment samples, we detected 597 mutations in 78 genes in 87 (92%) patients. In the matching CR samples, 62 (10%) and 82 (14%) mutations persisted at VAF≥2.5% and ≥1%, respectively, which corresponded to 43 (49%), 34 (39%), and 30 (34%) patients achieving MC2.5, MC1.0 and CMC, respectively. Table 1 shows the differential patterns of MC based on the mutations and pathways. Mutations associated with clonal hematopoiesis of indeterminate potential (CHIP), DNA methylation, and splicing pathways had low rate of MC, whereas mutations in transcription factors or receptor tyrosine kinase (RTK) had high rate of MC. Pts who achieved MC1.0 (median 31.2 vs. 12.5 months, P = 0.04) or CMC (median 31.2 vs. 12.5 months, P = 0.049) had significantly better relapse-free survival (RFS). Conclusions: Somatic mutations associated with CHIP, DNA methylation, and splicing pathways persisted frequently in CR samples suggesting preleukemic origin. Pts with deeper MC had significantly better RFS. Somatic mutation clearance may help risk prediction of AML.
|Gene||MC2.5 (%)||MC1.0 (%)||CMC (%)||Pathway||MC2.5 (%)||MC1.0 (%)||CMC (%)|