Pemigatinib for the treatment of myeloid/lymphoid neoplasms with FGFR1 rearrangement.

Introduction: Myeloid/lymphoid neoplasms with fibroblast growth factor receptor-1 (FGFR1) rearrangements (MLN^FGFR1) are rare entities with aggressive features and poor prognosis. Presentation is heterogeneous, ranging from myeloproliferative neoplasms (with or without eosinophilia) to T-cell lymphoma and acute leukemia. Historical treatments have been guided by the presenting phenotype with induction chemotherapy frequently used. Pemigatinib is a FGFR1-3 tyrosine kinase inhibitor that has demonstrated high complete hematologic and cytogenetic response rates in MLN^FGFR1.

Areas covered: We discuss the pathogenesis, presentation, and historical treatments for MLN^FGFR1, in addition to clinical data using pemigatinib and other targeted therapies. Discussion of the mechanism of action and adverse events is also included.

Expert opinion: Pemigatinib represents a significant advance in the management of MLN^FGFR1. High rates of complete hematologic and cytogenetic response have been observed. While direct comparative data are unavailable, outcomes appear favorable compared to conventional approaches. Long-term efficacy and tolerability are not yet known, and allogeneic hematopoietic stem cell transplant (alloHSCT) continues to be the treatment with the highest chance of long-term disease free survival in responding patients. Combinations of pemigatinib and chemotherapy, particularly for more aggressive phenotypes, warrant future investigation as does the use of pemigatinib maintenance following alloHSCT.