On August 26, the U.S. Food and Drug Administration (FDA) approved pemigatinib (Pemazyre), a selective fibroblast growth factor receptor (FGFR) inhibitor, for the treatment of adults with relapsed or refractory myeloid/lymphoid neoplasms with FGFR1 rearrangement. Myeloid/lymphoid neoplasms with FGFR1 rearrangement are extremely rare, aggressive blood cancers that may impact less than 1 in 100,000 people in the United States.
A patient with a myeloid/lymphoid neoplasm with FGFR1 rearrangement may present with bone marrow involvement with a chronic myeloid malignancy (such as myeloproliferative neoplasm [MPN], myelodysplastic syndrome/MPN) or a blast-phase malignancy (such as B- or T-cell acute lymphoblastic leukemia/lymphoma, acute myeloid leukemia, or mixed-phenotype acute leukemia). Bone marrow involvement may or may not be accompanied by extramedullary disease; some patients may present with extramedullary disease only.
Myeloid/lymphoid neoplasms with FGFR1 rearrangement are caused by chromosomal translocations involving the FGFR1 gene, with various partner genes resulting in constitutive activation of the FGFR1 receptor tyrosine kinase, impacting cell differentiation, proliferation, and survival. Patients often relapse because existing first-line therapies sometimes fail to induce durable clinical and cytogenetic responses.
FIGHT-203
The FDA approval was based on data from the phase II FIGHT-203 study (ClinicalTrials.gov identifier NCT03011372), a multicenter, open-label, single-arm trial that evaluated the safety and efficacy of pemigatinib in 28 patients with relapsed or refractory myeloid/lymphoid neoplasms with FGFR1 rearrangement. Patients could have relapsed after allogeneic hematopoietic stem cell transplantation or after a disease-modifying therapy, or were not a candidate for allogeneic hematopoietic stem cell transplantation or other disease-modifying therapies.
- Study participants included patients with documented myeloid/lymphoid neoplasms with an 8p11 translocation on conventional cytogenetics and/or an FGFR1 rearrangement on break-apart fluorescence in situ hybridization testing. (An FDA-approved test for detection of FGFR1 rearrangement in patients with relapsed or refractory myeloid/lymphoid neoplasms is not available.)
- In patients with chronic phase in the marrow with or without extramedullary disease (n = 18), the complete response rate was 78% (14 of 18; 95% confidence interval [CI] = 52%–94%). The median time to response was 104 days (range = 44–435 days). The median duration of complete response was not reached (range = 1+ to 988+ days).
- In patients with blast phase in the marrow with or without extramedullary disease (n = 4), two patients achieved a complete response (duration = 1+ and 94 days).
- In patients with extramedullary disease only (n = 3), one patient achieved a complete response (duration = 64+ days).
- For all patients (n = 28, including 3 without evidence of morphologic disease) the complete cytogenetic response rate was 79% (22 of 28; 95% CI = 59%–92%).
The most common (≥ 20%) adverse reactions were hyperphosphatemia (74%), nail toxicity (62%), alopecia (59%), stomatitis (53%), diarrhea (50%), dry eye (50%), fatigue (44%), rash (35%), abdominal pain (35%), anemia (35%), constipation (32%), dry mouth (32%), epistaxis (29%), retinal pigment epithelial detachment (26%), extremity pain (26%), decreased appetite (24%), dry skin (24%), dyspepsia (24%), back pain (24%), nausea (21%), blurred vision (21%), peripheral edema (21%), and dizziness (21%).
Srdan Verstovsek, MD, PhD
“In patients with relapsed or refractory myeloid/lymphoid neoplasms with FGFR1 rearrangement treated with pemigatinib in FIGHT-203, the high rate of complete response and complete cytogenetic response in patients with chronic-phase disease and the high rate of complete cytogenetic response in patients with blast-phase disease is clinically meaningful, especially in light of the lack of these specific responses with existing first-line treatments,” said Srdan Verstovsek, MD, PhD, Professor, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, and principal investigator for the FIGHT-203 study.
The supplemental new drug application or pemigatinib for the treatment of adults with relapsed or refractory myeloid/lymphoid neoplasms with FGFR1 rearrangement was reviewed by the FDA under Priority Review.
