Allogeneic HSCT prolonged RFS in NPM1-mutated AML

Allogeneic hematopoietic stem cell transplantation was associated with significantly improved RFS in patients with acute myeloid leukemia who harbored nucleophosmin-1 gene mutations, according to study results.

The lack of OS benefit with allogeneic hematopoietic stem cell transplantation (HSCT) in these patients may be due to the favorable outcomes after salvage treatment, researchers wrote.

Christoph Röllig, MD, of University Hospital Dresden in Germany, and colleagues evaluated data from 1,179 patients with intermediate-risk AML aged 18 to 60 years who were enrolled on the Study Alliance Leukemia AML 2003 trial. Researchers identified nucleophosmin-1 (NPM1) mutations in 375 (31.8%) of the patients, and 304 were eligible for the analysis.

Christoph Röllig

Seventy-seven patients had an HLA-identical sibling donor; of these, 55 were able to undergo transplantation at the time of first complete remission and seven underwent transplantation at the time of relapse. The other 227 patients did not have a sibling donor and received chemotherapy alone.

Complete remission occurred in 95% of patients with donors and 89% of patients without.

Median follow-up was 52 months.

Median RFS was 27 months among patients without a donor and was not yet reached among patients with a donor.

Seventy-one percent of patients with a donor achieved 3-year RFS compared with 47% of the patients without a matched donor (P=.005).

Median OS had not been reached in either cohort at the time of the analysis. Three-year OS rates did not differ significantly between patients who did and did not have a donor (70% vs. 60%; P=.114).

“The main reason for this finding is the persistent chemotherapy sensitivity of NPM1-mutant disease in the relapse setting, allowing the achievement of a second remission in 65% of patients by re-induction and subsequent salvage transplantation from an allogeneic donor in 47% of patients,” Röllig and colleagues wrote.

Researchers further evaluated data from 148 patients with normal karyotype who did not have the FLT3-ITD mutation. Forty-three of these patients had a sibling donor.

Significantly more patients in this donor cohort achieved 3-year RFS than those without a donor (83% vs. 53%; P=.004). More patients with a sibling donor also achieved 3-year OS, but this difference was not statistically significant (81% vs. 75%; P=.3).

“Our study suggests that allogeneic HSCT seems to represent a valuable consolidation choice for patients with NPM1-mutant AML in first complete remission if a sibling donor is available, especially in young patients with a relatively low risk of non-relapse mortality,” Röllig and colleagues wrote.

It is unlikely that a prospective randomized trial will be conducted to determine whether patients with NPM1 mutations should undergo transplantation, Edwin P. Alyea, MD, associate director of stem cell transplantation at Dana-Farber Cancer Institute, wrote in an invited commentary.

“Clinicians will need to decide on the basis of the available data,” Alyea wrote. “Further retrospective analyses will contribute to our understanding of the optimal post-remission therapy, and perhaps a meta-analysis of these studies will provide further clarity. The donor vs. no-donor design, when applied correctly, does seem to be a reasonable approach to clarify the role of allogeneic transplantation compared with other therapy options.”

For more information:

Alyea EP. J Clin Oncol. 2014;doi:10.1200/JCO.2014.58.6818.

Röllig Christoph. J Clin Oncol. 2014;doi:10.1200/JCO.2013.54.4973.

Disclosure: One researcher reports employment/leadership roles with and stock ownership in AgenDix GmbH.