HMAs in NPM1 mutated AML patients unfit for intensive chemotherapy

This month, in a Letter to the Editor of Haematologica, Pedro Henrique Prata from the Hématologie Clinique, Hôpital Saint Louis, Paris, France, and colleagues reported results from their retrospective study, which evaluated the outcomes of patients with nucleophosmin-1 (NPM1) mutated acute myeloid leukemia (AML) unfit for intensive chemotherapy (IC) who are treated with hypomethylating agents (HMAs).

In total, 71 NPM1 positive AML patients who were treated with HMAs between 2007 and 2016 in eight European and one American center were analyzed in this study.

Thirty-four patients (median age = 77 years; range 55–85) received upfront HMAs. They had been considered unfit for intensive chemotherapy based on age > 80, cardiac or other comorbidities, and according to each institution’s recommendations. Azacitidine (AZA) was administered in 17 patients, decitabine (DAC) in 10 patients, and seven patients received guadecitabine. Patients in this group were compared with 92 NPM1 negative AML patients treated upfront with azacitidine between 2007 and 2012.

Thirty-seven patients (median age = 65 years; range 36–87) received HMAs as second or subsequent line of treatment. Patients in this group had previously received anthracycline or cytarabine-based chemotherapy, seven patients had allogeneic, and one autologous stem cell transplantation. AZA was administered in 30 patients, DAC in seven patients and none of the patients received guadecitabine.

Key findings:

• Patients receiving HMAs as first line therapy
  • Overall response ratio (ORR): 45.5%
    • Complete response (CR): 23.5% (8/34)
    • Complete response with incomplete count recovery (CRi): 12% (4/34)
    • Partial response (PR): 9% (3/34)
  • Median overall survival (OS): 280 days
  • Median OS in NPM1 positive and negative patients (median age = 74 years): 280 vs 291 days, P = 0.53, respectively
  • Only one patient was alive after 2 years but relapsed and died at 24.5 months
• Patients receiving HMAs as second or subsequent line of therapy
  • ORR: 24.5%
    • CR: 21.5% (8/37)
    • CRi: 3% (1/37)
    • Median OS: 269 days

In summary, this is the first study evaluating HMAs in NPM1 positive AML. The results of this retrospective study indicate that HMAs did not yield positive results in terms of long-term survival as first-line treatment of NPM1 positive AML.  The authors suggested that NPM1 status should be added to first-line treatment decision factors in elderly AML. They further noted that “NPM1 status could contribute to physician’s decisions to administer IC rather than HMA when no major contraindications to IC exist.”