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NPM1-Positive/FLT3-ITD–Negative Genotype Not Associated With Significantly Better Prognosis in Older AML Patients

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Key Points

  • The presence vs absence of the NPM1-positive/FLT3-ITD–negative genotype was associated with a 2-year survival of 70% vs 32% among AML patients aged 55 to 65 years and 27% vs 16% among those aged ≥ 65 years.
  • On multivariate analysis, the presence of the genotype was a significant predictor of better overall survival among patients aged 55 to 65 years but not among older patients.

In a study reported in the Journal of Clinical Oncology, Ostronoff et al found that the presence of the NPM1-positive/FLT3-internal tandem duplication (ITD)–negative genotype—which is recognized as a marker of better prognosis in younger patients with acute myeloid leukemia—was not associated with significantly improved prognosis in older AML patients.

No Significant Benefit in Older Patients

Analysis of 156 patients aged ≥ 55 years with AML treated with intensive chemotherapy in Southwest Oncology Group (SWOG) trials showed that among those aged 55 to 65 years, the presence vs absence of the NPM1-positive/FLT3-ITD–negative genotype was associated with significantly better 2-year overall survival (70% vs 32%, P < .001). Among patients with the genotype, 2-year overall survival was better in those aged 55 to 65 years vs ≥ 65 years (70% vs 27%, P < .001). Among patients aged ≥ 65 years, the presence vs absence of the genotype was associated with nonsignificantly better 2-year overall survival (27% vs 16%, P = .33). In multivariable analysis, NPM1-positive/FLT3-ITD–negative genotype was independently associated with improved overall survival among patients aged 55 to 65 years (hazard ratio [HR] = 0.20, P = .002) but not among those aged ≥ 65 years (HR = 0.91, P = .82).

Validation Analysis

Validation analysis among 1,258 patients treated in UK National Cancer Research Institute/Medical Research Council trials confirmed the findings in the SWOG analysis, with patients with the NPM1-positive/FLT3-ITD–negative genotype who were aged 55 to 65 years having significantly better 2-year overall survival and relapse-free survival (both P  < .001) compared with those aged ≥ 65 years.

The investigators concluded: “NPM1-positive/FLT3-ITD–negative genotype remains a relatively favorable prognostic factor for patients with AML age 55 to 65 years but not in those age ≥ 65 years.”

Fabiana Ostronoff, MD, of Fred Hutchinson Cancer Research Center, is the corresponding author of the Journal of Clinical Oncology article.

The study was supported by grants from the National Cancer Institute. For full disclosures of the study authors, visit jco.ascopubs.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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