First-line pemigatinib in a myeloid/lymphoid neoplasm with FGFR1 rearrangement: shifting the current treatment paradigm

Myeloid/lymphoid neoplasms with FGFR1 rearrangement (MLNFGFR1) are rare, aggressive hematologic malignancies with limited treatment options. Although pemigatinib is approved for relapsed/refractory disease, evidence supporting its role in the frontline setting remains limited. We report a 69-year-old female with newly diagnosed MLNFGFR1 in blast phase, presenting with concurrent myeloproliferative neoplasm and T-lymphoblastic lymphoma. As the patient declined intensive chemotherapy, frontline pemigatinib was initiated in combination with intrathecal chemotherapy for central nervous system prophylaxis. A rapid hematologic response was achieved, followed by complete metabolic and cytogenetic responses. At 17 months after pemigatinib initiation, she remains in complete remission, with treatment-related toxicity being manageable through dose modifications and temporary interruptions. This case illustrates the potential of FGFR1 inhibition as a frontline therapeutic option in selected patients with MLNFGFR1, while highlighting the importance of careful toxicity management and the need for further studies to establish its role in this setting.