John Mascarenhas, MD, Director of the Adult Leukemia Program at The Tisch Cancer Institute at Mount Sinai, New York, commented on the implications of the FIGHT-203 trial, which evaluated pemigatinib in myeloid or lymphoid neoplasms.

Pemigatinib is an oral small-molecule receptor tyrosine kinase inhibitor of fibroblast growth factor receptors (FGFRs) 1 to 3. FGFR 1 to 3 signaling pathways are upregulated in a subset of hematologic malignancies involving rearrangements of chromosome 8p11 and classified by the World Health Organization as myeloid or lymphoid neoplasms with FGFR1 rearrangement. These rare and aggressive clonal neoplasms have a heterogeneous phenotype, including myeloproliferative features, acute myeloid and lymphoid leukemias, and lymphoma; they are frequently characterized by peripheral blood eosinophilia, extramedullary disease, and transformation to acute leukemia. They are associated with a poor prognosis and response to conventional chemotherapies, Dr. Mascarenhas explained.

John Mascarenhas, MD

‘Remarkable’ Findings From FIGHT-203

In the global multicenter, phase II FIGHT-203 study, 34 patients with myeloid or lymphoid neoplasms and FGFR1 involvement (most refractory to prior lines of therapy) were treated with pemigatinib for a median duration of 29 weeks. “Remarkably, the complete response rate was 65% and 77% for those with bone marrow involvement and/or extramedullary disease, respectively, and complete cytogenetic response in evaluable patients was 73% and 76%, respectively,” he noted.

Dr. Mascarenhas continued: “The safety profile was consistent with reports in solid malignancies and included gastrointestinal toxicity, treatment-emergent anemia, and hyperphosphatemia. Of note, the most common reason for study drug discontinuation was transition to hematopoietic stem cell transplantation.”

“Pemigatinib was approved in April 2020 by the U.S. Food and Drug Administration for previously treated patients with advanced or unresectable FGFR2-translocated cholangiocarcinoma. It may also offer a much-needed treatment option to extend benefit to patients with FGFR-rearranged myeloid or lymphoid neoplasms. In some cases, it may serve as a bridge to definitive therapy with stem cell transplant,” Dr. Mascarenhas commented. 

DISCLOSURE: Dr. Mascarenhas has received consulting fees from Incyte, Novartis, Roche, Geron, CTI Bio, Constellation, Sierra Oncology, Kartos, PharmaEssentia, Celgene, BMS, AbbVie, and Karyopharm.