An NPM1 mutation has prognostic significance and may be used to stratify patients with isocitrate dehydrogenase (IDH)-mutated acute myeloid leukemia (AML) for clinical trials, according to research published in Blood.

Researchers analyzed patients with IDH mutation subtypes to determine prognostic significance and outcomes after hematopoietic stem cell transplantation in patients with IDH-mutated AML treated with intensive chemotherapy.

The analysis included 319 patients from 3 ALFA prospective clinical trials. A total of 127 patients had IDH1 mutations, 135 had IDH2R140 mutations, and 57 had IDH2R172 mutations. The final analysis excluded 26 patients who received gemtuzumab or ozogamicin.

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A total of 76% of patients achieved complete remission (CR) or CR with incomplete platelet recovery (CRp) after 1 course of intensive chemotherapy, and 83% achieved CR/CRp after 2 courses of intensive chemotherapy.

Patients with an IDH1 and concomitant NPM1 mutation had higher CR/CRp than patients with NPM1 wild-type (94% vs. 66%; P =.0002). Patients with IDH2R140 and concomitant NPM1 mutation also had better survival than NPM1 wild-type (100% vs 82%; P =.0003).

Patients with IDH2R140-mutated AML with NPM1 mutations had prolonged overall survival (OS) and disease-free survival (DFS). Presence of DNMT3A mutations predicted worse OS.

No prognostic factors were associated with IDH2R172-mutated AML. No NPM1 mutations were found in patients with IDH2R172 mutations. Low platelet counts were associated with more advanced and resistant disease in these patients.

The authors also analyzed hematopoietic stem cell transplant (HSCT) in first CR for 197 patients with IDH mutations. A total of 71 patients eventually underwent HSCT. Patients who underwent HSCT in CR1 had prolonged OS and prolonged DFS. Patients with IDH1R132 mutations had an OS benefit, and patients with IDH2R172 mutations had a trend toward better DFS.

Overall, the authors found that NPM1 was a prognostic factor for patients with IDH1 and IDH2R140 mutations. Based on these results, future trials should consider stratifying patients with IDH-mutated AML based on their NPM1 mutational status. Additionally, HSCT should be incorporated into the treatment strategy.

Disclosure: The study author(s) declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Duchmann M, Micol JB, Duployez N, et al. Prognostic significance of concurrent gene mutations in intensively treated patients with IDH-mutated AML: an ALFA study. Blood. 2021;137(20):2827-2837. doi:10.1182/blood.2020010165