Entirely Venetoclax-Based Nonintensive Treatment Regimen for Newly Diagnosed NPM1-Mutated Acute Myeloid Leukemia in the ELN Favorable-Risk Group

The NPM1 mutation is one of the most common mutation types in acute myeloid leukemia (AML) and has shown a good response to venetoclax-based treatment. However, there are currently no prospective clinical trials for a nonintensive treatment regimen that is entirely venetoclax-based in NPM1-mutated AML. We conducted a single-arm, multicenter clinical study of venetoclax in combination with hypomethylating agents (decitabine or azacitidine) for the treatment of newly diagnosed NPM1-mutated AML in the ELN favorable risk group.

A total of 14 patients, including 9 males and 5 females, have been enrolled from 4 medical centers. The median age is 57 years (range, 30-76), and 12 patients were fit, while 2 were unfit. All the patients were diagnosed as AML according to the WHO 2022 criteria, while 11 cases were diagnosed with AML, 1 case with MDS-EB1, and 2 cases with CMML according to ELN 2022 diagnostic criteria. Twelve (85.7%) had NPM1 type A transcripts, 1 (7.1%) had type B, and 1 (7.1%) had a rare type. None of the patients had high-risk karyotypes, but 6 (42.9%) patients had recurrent MDS-related changes (MRCs).

The median follow-up time was 3.0 months (range, 0.5-25.0), with a median of 3 (range, 0-11) treatment cycles completed. All 12 patients who completed at least 1 treatment cycle achieved a CR/CRi rate of 100% after just 1 cycle. Of these patients, 9 (75%) achieved bone marrow (BM) molecular MRD-negative remission after a maximum of 4 treatment cycles. The median number of cycles to achieve molecular negativity was 2 (range, 1-4), with a median time to molecular negativity of 2 months (range, 1-7).

One patient experienced molecular relapse and had to withdraw from the cohort after 10 treatment cycles, while another patient had to discontinue due to severe infection. In general, NPM1-mutated patients in a favorable risk group who received a venetoclax-based nonintensive treatment regimen were able to achieve early BM molecular remission, though longer-term relapse outcomes remain to be seen.

No relevant conflicts of interest to declare.

Venetoclax is approved for the treatment of newly diagnosed acute myeloid leukemia in adults aged 75 years or older who are ineligible for standard intensive induction chemotherapy due to comorbidities.