Measurable residual disease (MRD) can be used to guide prophylactic treatment after allogeneic haematopoietic stem cell transplantation (HSCT) in patients with FLT3-ITD positive acute myeloid leukaemia (AML) to achieve best outcomes, researchers report.
A new, personalised treatment paradigm involving frequent MRD testing pre- and post- HSCT could inform clinicians on which patients would most likely benefit from maintenance therapy with an FLT3 inhibitor, and thus also save those unlikely to benefit from suffering treatment-related toxicities, the data indicate.
International guidelines recommend use of post-HCT maintenance with FLT3 inhibitors to reduce the risk of relapse in AML patients, and some guidelines back off-label use of sorafenib in this clinical setting (link here), as long as patients demonstrate adequate engraftment and start therapy no longer than four months after transplant.
However, findings of a study assessing the FLT3 inhibitor gilteritinib, published in the Journal of Clinical Oncology (link here), suggest that only patients who exhibit detectable MRD peri-transplant stand to benefit from such an approach.
In the international Phase III MORPHO trial, 356 patients with FLT3-ITD AML in first remission were randomly assigned to receive either gilteritinib or placebo post-HSCT.
More than half of patients had FLT3-ITD AML MRD pre- or post-HCT detected by highly sensitive new assays using sequential polymerase chain reaction (PCR) and next-generation sequencing (NGS).
Overall, although relapse-free survival (RFS) was higher in the gilteritinib arm, the difference was not statistically significant (hazard ratio [HR] 0.7 [95% CI, 0.459 to 1.005]; two-sided p=0.0518).
However, a significant RFS benefit from the drug was observed in patients with detectable peri-transplant MRD (HR 0.5 [95% CI, 0.316 to 0.838]; p=0.0065), and not in those without detectable MRD (HR 1.213 [95% CI, 0.616 to 2.387]; p=0.575).