NPM1,   General AML

Karyotype plus NPM1 Mutation Status Defines a Group of Elderly Patients with AML (≥60 Years) who Benefit from Intensive Post-Induction Consolidation Therapy

Sperr WR et al. of the Medical University of Vienna, conducted an analysis in 192 elderly patients with de novo AML treated with intensive chemotherapy.  This study aimed to provide physicians with data to enable them to make evidence-based decisions on treatment options to complement the patients’ cytogenic characteristics.

The groups analyzed included patients with CN/Mkneg-NPM1mut, CBF AML, CN/Mkneg-NPM1wt and Mkpos AML. Their findings were published in Am J Hematol. 2016 Sep 19 and provide useful insights on which type of chemotherapy to adopt for the different patient types. In addition, for whom a hematopoietic-stem-cell-transplantation is suitable for in relation to the patients' cytogenic characteristics.

Please see their published abstract with their recommendations below.

 

Abstract

Although it is generally appreciated that a subset of elderly patients with acute myeloid leukemia (AML) may benefit from intensive consolidation, little is known about variables predicting such benefit. We analysed 192 consecutive patients with de novo AML aged ≥60 years who were treated with intensive chemotherapy. One-hundred-fifteen patients (60%) achieved complete hematologic remission (CR). Among several parameters, the karyotype was the only independent variable predicting CR (p<0.05). Ninety-two percent (105/115) of the CR-patients received up to 4 consolidation cycles of intermediate dose ARA-C. Median continuous CR (CCR) and disease-free survival (DFS) were 1.3 and 1.1 years, respectively. CCR, DFS, and survival at 5 years were 23%, 18%, and 15%, respectively. Only karyotype and mutated NPM1 (NPM1mut) were independent predictors of survival. NPM1mut showed a particular prognostic impact in patients with normal (CN) or non-monosomal (Mkneg) karyotype by HOVON-criteria, or intermediate karyotype by SWOG-criteria. The median CCR was 0.94, 1.6, 0.9, and 0.5 years for core-binding-factor, CN/Mkneg-NPM1mut, CN/Mkneg-NPM1-wild-type AML, and AML with monosomal karyotype, respectively, and the 5-year survival was 25%, 39%, 2%, and 0%, respectively (p<0.05). Similar results (0.9, 1.5, 0.9, and 0.5 years) were obtained using modified SWOG criteria and NPM1 mutation status (p<0.05). In summary, elderly patients with CN/Mkneg-NPM1mut or CBF AML can achieve long term CCR when treated with intensive induction and consolidation therapy whereas most elderly patients with CN/Mkneg-NPM1wt or Mkpos AML may not benefit from intensive chemotherapy. For these patients either hematopoietic-stem-cell-transplantation or alternative treatments have to be considered. 

References
  1. Sperr W.R. et al. Karyotype plus NPM1 Mutation Status Defines a Group of Elderly Patients with AML (≥60 Years) who Benefit from Intensive Post-Induction Consolidation Therapy. Am J Hematol. 2016 Sep 19. DOI: 10.1002/ajh.24560. [Epub ahead of print]
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