FDA Approves Pemigatinib for Myeloid/Lymphoid Neoplasms With FGFR1 Rearrangement

The FDA Friday approved pemigatinib (Pemazyre), a selective fibroblast growth factor (FGFR) inhibitor, to treat adults who have relapsed or refractory (R/R) myeloid/lymphoid neoplasms (MLNs) with FGFR1 rearrangement. These aggressive cancers are very rare and may affect less than 1 in 100,000 people in the United States, according to a statement from the therapy’s manufacturer, Incyte.

Pemigatinib was previously approved for previously treated patients with R/R unresectable, locally advanced or metastatic cholangiocarcinoma with a FGFR2 fusion or rearrangement, as determined by an FDA-approved test.

“The approval of Pemazyre represents an important treatment advancement for people living with MLNs with FGFR1 rearrangement who currently have limited treatment options,” Hervé Hoppenot, CEO of Incyte, said in a statement. “These are complex hematologic malignancies with a range of presentations, and this approval highlights Incyte’s continued leadership and commitment to advancing care for patients with rare blood cancers.”

Patients who have an MLN with FGFR1 rearrangement may have bone marrow involvement with a chronic myeloid malignancy, such as myelodysplastic syndrome, or blast phase diseases, such as acute lymphoblastic leukemia/lymphoma.

These neoplasms are caused chromosomal translocations involving the FGFR1 gene, with other genes affecting cell differentiation and growth. Thus, if first-line does not create a cytogenetic response, relapse can occur.

Approval followed release of data from the phase 2 FIGHT-203 study, a multicenter open-label, single-arm trial involving 28 patients; the trial evaluated the safety and efficacy of pemigatinib with relapsed or refractory MLNs with FGFR1 rearrangement. Patients could have relapsed after allogeneic hematopoietic stem cell transplantation (allo-HSCT) or after a disease modifying therapy, or patients were not a candidate for allo-HSCT or other disease modifying therapies. Results showed the following:

In patients with chronic phase in the marrow with or without extramedullary disease (EMD), (N = 18), the complete response (CR) rate was 78%. The median time to response of CR was 104 days (range, 44 to 435 days). The median duration of CR was not reached (range, 1+ to 988+ days).

• In patients with blast phase in the marrow with or without EMD (N = 4), 2 patients achieved a CR (duration: 1+ and 94 days).
• In patients with EMD only (N = 3), one patient achieved a CR (duration: 64+ days).
• For all patients (N = 28), including 3 patients without evidence of morphologic disease, the complete cytogenetic response rate was 79%.

Common adverse reactions appearing in at least 20% of the patients 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%).

“In patients with relapsed or refractory MLNs with FGFR1 rearrangement treated with Pemazyre 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,” Srdan Verstovsek, MD, PhD, professor, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, in Houston, Texas, and principal investigator for FIGHT-203, said in the statement.