Page 55 - Haematologica - Vol. 105 n. 6 - June 2020

EBMT ALWP recommendation for allo-SCT for FLT3 AML
rant further investigation in larger prospective studies. Grade level B-II
• Maintenance therapy should be initiated as soon as possible after disease evaluation, including MRD assess- ment (whenever feasible), especially in patients with MRD-positive AML before or after allo-SCT, provided there is adequate hematologic reconstitution. Grade level B-II
• Sorafenib should be transiently discontinued in the case of GvHD requiring systemic treatment with corticos- teroids, but may be cautiously resumed once remission of GvHD is documented. Grade level B-III
• If choosing sorafenib, the recommended post-trans- plant maintenance dose is 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. Grade level B-III
• One potential challenge is the lack of approval of sorafenib for AML and its off-label use may not be reim- bursed in many/most countries. Ongoing studies will determine the role and modalities of use of midostaurin, gilteritinib or other FLT3 inhibitors in this setting.
• The duration of maintenance therapy is not firmly established, but a minimum of 2 years is recommended, depending on tolerance. Grade level B-III
• Monitoring is recommended for potential drug-drug interactions and long-term side effects.
Aspects to be resolved
• Standardization of FLT3-ITD allelic ratio in terms of technique and cut-off level
• Indication for allo-SCT in patients with FLT3-ITD AML who belong to the ELN intermediate risk group (high allelic ratio ≥0.5 with concomitant NPM1 mutation) and who achieve MRD negativity.
• Time of withdrawal of immunosuppression
• Pre-emptive versus prophylactic donor lymphocyte infusion
• Post-transplant maintenance with FLT3 inhibitors out- side FLT3-ITD AML (immunomodulatory and off-target effects)
• Impact of post-transplant maintenance therapy on immune reconstitution and environment
• Combination of post-transplant FLT3 inhibitors with other drugs such as hypomethylating agents
• Monitoring of patients receiving post-transplant FLT3 inhibitors for potential extramedullary relapse or aggres- sive clone selection.
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