FDA Gives Pemigatinib Greenlight for FGFR1 Rearranged Myeloid/Lymphoid Neoplasms


Pemigatinib has received FDA approval for relapsed or refractory myeloid/lymphoid neoplasms and FGFR1 rearrangement. Patients receiving pemigatinib will require monitoring for ocular toxicities and high phosphate levels.

The FGFR inhibitor pemigatinib (Pemazyre)was approved for patients with relapsed or refractory myeloid/lymphoid neoplasms (MLNs) with FGFR1 rearrangement, according to a news release.1

Findings from the phase 2 FIGHT-203 study (NCT03011372) supported the regulatory decision. This multicenter open-label, single-arm trial assessed the agent’s safety and efficacy in 28 patients with relapsed or refractory disease and an FGFR1 rearrangement. Patients were eligible if they had received either an allogeneic hematopoietic stem cell transplantation (allo-HSCT) or disease modifying therapy and had disease relapse or were not a candidate for allo-HSCT or another disease modifying therapies.

The complete cytogenetic response rate across all patients, including 3 without evidence of morphologic disease was 79% (95% CI, 59%-92%).

The complete response (CR) rate among patients with chronic phase in the marrow with or without extramedullary disease (EMD; n = 18) was 78% (95% CI, 52%-94%). Among these same patients, the median time to response was 104 days (range, 44-435) and the median duration of response (DOR) was not reached.

Fifty percent of patients with blast phase in the marrow achieved a CR (n = 4), with or without EMD. The DOR for these patients was 1+ and 94 days, respectively. In patients with EMD alone (n = 3), 1 patient achieved a CR with a DOR of 64+ days.

Myeloid and lymphoid neoplasms with FGFR1 rearrangements are rare and aggressive forms of blood cancer that impact less than 1 in 100,000 individuals in the United States. Unfortunately, patients often relapse because frontline treatment fails to induce durable clinical and cytogenic responses. This regulatory decision marks the approved first targeted therapy for this patient population.

“In patients with relapsed or refractory MLNs 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,” Srdan Verstovsek, MD, PhD, a professor in the Department of Leukemia, Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center in Houston, and principal investigator for the FIGHT-203 study, said in a press release.

Ocular Toxicities

Pemigatinib has been associated with retinal pigment epithelial detachment (RPED), a condition which many cause symptoms such as blurred vision, visual floaters, or photopsia.

Although the rate of asymptomatic RPED is unknown, among 635 who received a starting dose of 13.5 mg of pemigatinib, 11% developed confirmed RPED, of which 1.3% of events were categorized as grade 3/4. The median onset time was 56 days. RPED resulted in dose interruption, reduction, and discontinuation in 3.1%, 1.3%, and 0.2% of patients, respectively. Dose modifications resolved 76% of RPED cases.

Prior to treatment, patients should undergo a comprehensive ophthalmological examination. Once treatment begins, assessments should be conducted every 2 months for the first 6 months of treatment, and every 3 months thereafter. Ophthalmologic specialists should be consulted immediately if visual symptoms occur, and follow-up should continue every 3 weeks until symptoms resolve. If there is no resolution, treatment may need to be discontinued.

Dry eye occurred in 31% of patients; 1.6% of whom reported grade 3 or 4 severity. Patients should be treated with ocular demulcents as needed.


Laboratory values showed that 93% of patients developed hyperphosphatemia. As a result, 33% of patients receiving the therapy required phosphate lowering therapy. The median onset time was 8 days (range 1-169).

Patients must be monitored for hyperphosphatemia while on treatment. If serum phosphate levels surpass 5.5 mg/dL, a low phosphate diet is advised. If levels surpass 7 mg/dL, phosphate lowering therapy should be administered and treatment should be withheld, reduced, or—depending on the duration and severity of the hyperphosphatemia—permanently discontinued.

Overall Safety Profile

Severe adverse effects (AEs) resulting in fatalities included acute kidney injury, multiple organ dysfunction syndrome, and malignant neoplasm progression. AEs resulting in permanent discontinuation occurred in 12% of patients, these reactions included cardiac failure, multiple organ dysfunction syndrome, blood alkaline phosphatase increase, and calciphylaxis.

The most common AEs of any grade included 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%).

Overall, dose reductions because of AEs were required in 80% of patients who started on the recommended dose (13.5 mg)

Patients receiving pemigatinibshould avoid the strong or moderate use of CYP3A inhibitors. If CYP3A inhibitors cannot be avoided, the dose of pemigatinib should be reduced.


Incyte announces FDA approval of Pemazyre (pemigatinib) as the first and only targeted treatment for myeloid/lymphoid neoplasms (MLNs) with FGFR1 rearrangement. News release. Incyte. August 26, 2022. Accessed August 26, 2022. https://bwnews.pr/3wzSxxH

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