AML-164: Next-Generation Sequencing (NGS) Profile by Illumina Trusight Myeloid Sequencing Panel (TSM) in a Cohort of Peruvian Patients with AML/MDS

Abstract

Precise identification of AML/MDS biology and the identification of pathogenic mutated genes is relevant for risk stratification and therapy strategy, mainly for cases where targeted therapies is a must. Here, we describe the main pathogenic mutated genes and clinical outcomes in a cohort of Peruvian patients diagnosed with AML/MDS studied at diagnosis with the Illumina TruSight Myeloid Sequencing Panel (TSM), which includes 54 genes. In this report, we showed 20 consecutive AML/MDS cases treated in 2 different medical centers in Lima from January 2016 until March 2020. F/M ratio 1/4, median age 64 years (range, 16-87), number of cases were AML=12 and MDS=8. Abnormal vs diploid karyotype ratio was 1/4 (only four cases with abnormal karyotype). Median number of pathogenic mutated genes was 3 (range, 0-15). Most common (≥20%) pathogenic mutated genes expressed were BCOR, CUX1, ETV6/DEL, KMT2A, NOTCH1, NRAS, RAD21, STAG2, and TP53. Response rates were as follows: 45% complete (9/20), 15% partial (3/20), 25% non-response (5/20), and 15% non-evaluable (3/20). At a median follow-up of 12.0 months, the median overall survival (OS) was 32.88 ± 4.75 months for the entire cohort; for the AML and MDS cases, mean OS were 26.7 ± 4.4 and 32.8 ± 7.2 months, respectively (Log Rank 0.001; p=0.969). Mutated TP53 was detected in 5 AML/MDS cases with no therapy response in 4 that had already died with a median OS of 3.1 months (range, 0.8-36.6). We analyzed if ≥4 or ≥3 mutated genes impact on OS. We found a trend (non-significant) of longer OS for cases with < 4 vs ≥4 pathogenic mutated genes (37.7 ± 5.2 vs 26.0 ± 6.7; Log Rank 1.64; p=0.2) and longer OS for cases with <3 vs ≥3 pathogenic mutated genes (37.7 ± 5.2 vs 29.1 ± 6.0; Log Rank 0.834; p=0.36). NGS for AML/MDS is an important tool at diagnostic, assessment, and risk stratification in our series of cases. Only 9 over 53 genes were detected in ≥20% of cases. TP53 was related with a high therapy failure response and short OS for AML/MDS cases. Number of pathogenic mutated genes ≥4 or ≥3 by TSM showed a tendency for lower OS. Precise identification of AML/MDS biology and the identification of pathogenic mutated genes is relevant for risk stratification and therapy strategy, mainly for cases where targeted therapies is a must. Here, we describe the main pathogenic mutated genes and clinical outcomes in a cohort of Peruvian patients diagnosed with AML/MDS studied at diagnosis with the Illumina TruSight Myeloid Sequencing Panel (TSM), which includes 54 genes. In this report, we showed 20 consecutive AML/MDS cases treated in 2 different medical centers in Lima from January 2016 until March 2020. F/M ratio 1/4, median age 64 years (range, 16-87), number of cases were AML=12 and MDS=8. Abnormal vs diploid karyotype ratio was 1/4 (only four cases with abnormal karyotype). Median number of pathogenic mutated genes was 3 (range, 0-15). Most common (≥20%) pathogenic mutated genes expressed were BCOR, CUX1, ETV6/DEL, KMT2A, NOTCH1, NRAS, RAD21, STAG2, and TP53. Response rates were as follows: 45% complete (9/20), 15% partial (3/20), 25% non-response (5/20), and 15% non-evaluable (3/20). At a median follow-up of 12.0 months, the median overall survival (OS) was 32.88 ± 4.75 months for the entire cohort; for the AML and MDS cases, mean OS were 26.7 ± 4.4 and 32.8 ± 7.2 months, respectively (Log Rank 0.001; p=0.969). Mutated TP53 was detected in 5 AML/MDS cases with no therapy response in 4 that had already died with a median OS of 3.1 months (range, 0.8-36.6). We analyzed if ≥4 or ≥3 mutated genes impact on OS. We found a trend (non-significant) of longer OS for cases with < 4 vs ≥4 pathogenic mutated genes (37.7 ± 5.2 vs 26.0 ± 6.7; Log Rank 1.64; p=0.2) and longer OS for cases with <3 vs ≥3 pathogenic mutated genes (37.7 ± 5.2 vs 29.1 ± 6.0; Log Rank 0.834; p=0.36). NGS for AML/MDS is an important tool at diagnostic, assessment, and risk stratification in our series of cases. Only 9 over 53 genes were detected in ≥20% of cases. TP53 was related with a high therapy failure response and short OS for AML/MDS cases. Number of pathogenic mutated genes ≥4 or ≥3 by TSM showed a tendency for lower OS.