Page 54 - Haematologica - Vol. 105 n. 6 - June 2020

A. Bazarbachi et al.
ed AML patients, however, are not currently receiving midostaurin, at least outside the USA and some other countries; therefore, for the foreseeable future, patients may still benefit from sorafenib maintenance treatment after allo-SCT.
Summary of position statement (Table 1)
1- Indications for allogeneic stem-cell transplantation in FLT3-internal tandem duplication acute myeloid leukemia
• The indication for allo-SCT is controversial in patients with FLT3-ITD who belong to the ELN favorable risk group (low allelic ratio <0.5 with concomitant NPM1 mutation) and who achieve MRD negativity. Allo-SCT may be delayed until first relapse as recommended by the ELN or performed in CR1 as allowed by NCCN guide- lines. Grade level C-II
• In general, all other patients with FLT3-ITD AML should be considered for allo-SCT in CR1 if feasible. Grade level B-II
2- Modalities of hematopoietic stem cell transplantation
• Donors should be selected according to EBMT general guidelines83 including the potential use of cord blood grafts whenever indicated. Grade level B-II
• In vivo T-cell depletion decreases the risk of chronic GvHD, without apparently increasing the risk of relapse, in FLT3-ITD AML and is therefore an option in this set- ting. Grade level B-II
• The choice of conditioning has no direct link with FLT3-ITD mutation and should be adapted to other indi- vidual risk factors such as age, disease status at transplant, and donor type. Grade level B-II
3- Post-transplant maintenance for FLT3-internal tan- dem duplication acute myeloid leukemia
• Post-transplant maintenance therapy with a FLT3 inhibitor for patients who have undergone allo-SCT for FLT3-ITD AML is recommended (except for patients with active acute GvHD). In the absence of an appropriate clin- ical trial, sorafenib could be considered as the preferred option, but other FLT3 inhibitors are attractive and war-
Table 1. Summary of the European Society for Blood and Marrow Transplantation position statement on allogeneic hematopoietic stem-cell trans- plantation in FLT3-internal tandem duplication acute myeloid leukemia.
Indication for allo-SCT in FLT3 mutated AML
Modalities of allo-SCT
Post-transplant maintenance
Transplant indication is controversial in patients with FLT3-ITD who belong to the ELN favorable risk group (low allelic ratio <0.5 with concomitant NPM1 mutation) and who achieve MRD negativity. Allo-SCT may be delayed until first relapse as recommended by the ELN or performed in CR1 as allowed by NCCN guidelines.
In general, all other patients with FLT3-ITD should be considered for allo-SCT in CR1 if feasible.
Donor selection according to EBMT general guidelines.
In vivo T-cell depletion decreases the risk of chronic GVHD without an apparent increase in the risk of relapse in FLT3 mutated AML and is therefore an option in this setting.
The choice of conditioning has no direct link with FLT3 mutation and should be adapted to other individual risk factors such as age, disease status at transplant, and donor type.
Post-transplant systemic maintenance therapy with a FLT3 inhibitor for patients who underwent allo-SCT for FLT3-ITD AML is recommended (except for patients with active acute GvHD).
In the absence of an appropriate clinical trial, sorafenib could be considered as the preferred option, but the role of other FLT3 inhibitors warrants investigation.
Maintenance treatment should be initiated as soon as possible after disease evaluation, including MRD assessment, especially in patients with MRD-positive AML before or after allo-SCT, provided there is adequate hematologic reconstitution.
The recommended post-transplant maintenance is sorafenib at a dose of 400 mg/day in two divided doses. Patients with MRD-positive disease may receive 800 mg/day in two divided doses, to be adapted according to tolerance. Sorafenib should be transiently discontinued in the case of GvHD requiring systemic treatment with corticosteroids, but may be cautiously resumed once remission of GvHD is documented.
Ongoing studies will determine whether midostaurin, gilteritinib or other FLT3 inhibitors will become additional alternatives in this setting.
Maintenance therapy duration is not firmly established, but a minimum of 2 years is recommended, depending
on tolerance.
Allo-SCT: allogeneic hematopoietic stem cell transplantation; FLT3: FMS-like tyrosine kinase 3; AML: acute myeloid leukemia; FLT3-ITD: FLT3-internal tandem duplication; ELN: European LeukemiaNet; NPM1: Nucleophosmin 1; MRD: minimal residual disease; CR1: first complete remission; NCCN: National Comprehensive Cancer Network; EBMT: European Society for Blood and Marrow Transplantation; GvHD: graft-versus-host disease..
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