6014 - Impact of FLT3-ITD mutation on post-transplant outcome of adult AML is modified by the concomitant NPM1 mutation and pre-transplant remission status: A report from Taiwan Bone Marrow Transplant Registry (TBMTR)

Background

The impact of FLT3ITD^mut on post-transplant outcome of adult AML remains controversial. A decreased leukemia-free survival (LFS) after allogeneic hematopoietic stem cell transplantation (HSCT) for adult AML in complete remission (CR) was observed in EBMT analysis but not CIBMTR. The impact of FLT3ITD^mut on AML patients in later disease stage, as well as the influence of concurrent NPM1 mutation on post-transplant outcome, is less well studied.

Methods

In this study, only adults aged ≥ 18 years with a diagnosis of de novo AML who received allogeneic peripheral blood stem cell transplantation and with known FLT3ITD and NPM1 status in the registry were included. Kaplan-Meier estimates were used to calculate LFS and overall survival (OS). Multivariate analyses for LFS and OS were performed using Cox proportional hazards model.

Results

For patients who received transplant in CR1, the 2 year LFS, OS, and relapse incidence (RI) were 33.1%, 48.7%, and 56%, respectively, for patients of FLT3ITD^mutNPM1^wt, which are much inferior to patients of FLT3ITD^mutNPM1^mut (74.3%, 77.8%, and 25.7%, respectively) and patients of FLT3ITD^wt (53.5%, 71%, and 37.3%, respectively). In multivariate analysis, patients of FLT3ITD^mutNPM1^wt, but not patients of FLT3ITD^mutNPM1^mut, were associated with significant poor LFS (HR 2.672, p = 0.007) and OS (HR 2.439, p = 0.038) compared with patients of FLT3ITD^wt. For patients who received transplant after CR1, FLT3ITD^mut was associated with significant poor LFS (HR 1.775, p = 0.013) and OS (HR 1.716, p = 0.028) compared with patients of FLT3ITD^wt. NPM1 mutation dose not influence the outcome.

Conclusions

For patients in CR1, the impact of FLT3ITD is markedly modified by NPM1 status. The post-transplant outcome remains poor for patients of FLT3ITD^mutNPM1^wt and highlights the need for a novel approach (such as maintenance FLT3ITD inhibitor after transplant). For patients after CR1, the post-transplant outcome is very poor for patients of FLT3ITD^mut and is independent of NPM1 status.

Clinical trial identification

Editorial acknowledgement

The author thanks all the centers participating in the TBMTR. The report is on behalf of the Taiwan society of blood and bone marrow transplantation.

Legal entity responsible for the study

The author.

Funding

Has not received any funding.

Disclosure

The author has declared no conflicts of interest.