Futibatinib as a bridge to transplantation and post-transplant maintenance in blast-phase MLN-ZMYM2::FGFR1

Myeloid/lymphoid neoplasms with FGFR1 rearrangement (MLN-FGFR1) are rare, aggressive hematologic malignancies for which allogeneic hematopoietic cell transplantation (allo-HCT) remains the only potentially curative option. Pemigatinib, a reversible FGFR1-3 inhibitor, has substantial activity in chronic phase but lower efficacy in blast phase (BP). Data on futibatinib, an irreversible FGFR1-4 inhibitor, in BP MLN-FGFR1 are lacking. We report a 60-year-old man with MLN-ZMYM2::FGFR1 presenting in myeloid BP with extensive extramedullary disease (EMD) that was clinically refractory to induction chemotherapy. Initiation of off-label futibatinib was followed by rapid clinical improvement, complete cytogenetic remission (CCyR) and complete metabolic response (CMR), enabling bridging to allo-HCT from a mismatched unrelated donor. Futibatinib was subsequently continued as post-transplant maintenance with dose escalation and later combined with donor lymphocyte infusions (DLI). At last follow-up (day +497), the patient maintained a CMR and remained in CCyR with full donor chimerism, although ZMYM2::FGFR1 transcripts were still detectable at low levels in the bone marrow by droplet digital PCR. Next-generation sequencing additionally identified a germline DDX41 variant of uncertain significance, a finding potentially relevant to donor selection. To our knowledge, this is the first report of futibatinib used both as a bridge to transplantation and as post-transplant maintenance in BP MLN-FGFR1 with EMD. Although futibatinib's contribution cannot be separated from that of conditioning, graft-versus-leukemia activity and DLI, these hypothesis-generating findings provide support for further evaluation of irreversible FGFR1 inhibition in MLN-FGFR1.