The FDA has approved pemigatinib (Pemazyre®, Incyte Corporation) for the treatment of relapsed or refractory myeloid/lymphoid neoplasms (MLNs) with a fibroblast growth factor receptor 1 (FGFR1) rearrangement. This is the first approval and only targeted treatment for MLNs with a FGFR1 rearrangement.
"Myeloid/lymphoid neoplasms with a FGFR1 rearrangement comprise rare hematologic neoplasms belonging to the World Health Organization major category of fusion tyrosine kinases typically associated with eosinophilia," said Jason Gotlib, MD, Professor of Medicine at Stanford Medicine, and colleagues, in their abstract of the FIGHT-203 (NCT03011372) study, on which approval was based. "Given the poor prognosis of MLNs with a FGFR1 rearrangement and the potential for transformation to blast phase, a primary goal is to achieve deep responses to bridge patients to allogeneic hematopoietic stem cell transplant."
Safety and efficacy were measured in the phase 2, multicenter, open-label, single-arm trial, where 28 adult patients with MLNs with FGFR1 rearrangement were given 13.5 mg of pemigatinib once daily on a 21-day cycle, either on a continuous schedule, or an intermittent schedule where the patient would be on treatment for two weeks and off for one week. Treatment continued until disease progression or unacceptable toxicity or until patients were able to receive allogeneic hematopoietic stem cell transplantation (allo-HSCT).
The primary end point measured was complete response, including time to response and duration of response, with a key secondary end point of complete cytogenetic response. Complete response was achieved in 78% of patients (14 out of 18) with chronic phase in the marrow with or without extramedullary disease (EMD). For this group, the median time to complete response was 104 days, and the median duration of response was not reached (range 1+ to 988+ days). Complete response was also achieved in 2 out of 4 patients with blast phase in the marrow with or without EMD, and in 1 out of 3 patients with EMD only. Complete cytogenetic response was 79% for all 28 patients.
The most common adverse events in ≥20% of patients being treated with pemigatinib for MLNs with a FGFR1 rearrangement were hyperphosphatemia, nail toxicity, alopecia, stomatitis, diarrhea, dry eye, fatigue, rash, abdominal pain, anemia, constipation, dry mouth, epistaxis, serous retinal detachment, extremity pain, decreased appetite, dry skin, dyspepsia, back pain, nausea, blurred vision, peripheral edema, and dizziness. The most common grade 3 or 4 laboratory abnormalities in ≥10% of patients were decreased phosphate, decreased lymphocytes, decreased leukocytes, decreased platelets, increased alanine aminotransferase, and decreased neutrophils. When necessary, proper dose reduction due to high toxicity is detailed in the prescribing information.
"Pemigatinib is the first therapy to demonstrate durable and high rates of complete response and complete cytogenetic response in patients with MLNs with a FGFR1 rearrangement, most of whom had progressed on prior therapies including intensive chemotherapy or HSCT," concluded Dr. Gotlib and colleagues in their report. "These results suggest that pemigatinib may offer a long-term treatment option for patients with MLNs with a FGFR1 rearrangement ineligible for HSCT or may facilitate bridging to HSCT in eligible patients."
The recommended dosage of pemigatinib for adult patients being treated for MLNs with a FGFR1 rearrangement is 13.5 mg once daily on continuous schedule until disease progression or unacceptable toxicity.
For More Information
Gotlib J, Kiladjian JJ, Vannucchi A, et al (2021). A phase 2 study of pemigatinib (FIGHT-203; INCB054828) in patients with myeloid/lymphoid neoplasms (MLNs) with fibroblast growth factor receptor 1 (FGFR1) rearrangement (MLNFGFR1). Blood, 138(suppl_1): 385. DOI:10.1182/blood-2021-148103
Clinicaltrials.gov (2022). A study to evaluate the efficacy and safety of pemigatinib (INCB054828) in subjects with myeloid/lymphoid neoplasms with FGFR1 rearrangement - (FIGHT-203). NLM identifier: NCT03011372.
BusinessWire (2022). Incyte announces FDA approval of Pemazyre® (pemigatinib) as the first and only targeted treatment for myeloid/lymphoid neoplasms (MLNs) with FGFR1 rearrangement. Available at: https://www.businesswire.com/news/home/20220826005244/en/Incyte-Announces-FDA-Approval-of-Pemazyre%C2%AE-pemigatinib-as-the-First-and-Only-Targeted-Treatment-for-MyeloidLymphoid-Neoplasms-MLNs-with-FGFR1-Rearrangement
US Food and Drug Administration (2022). FDA approves pemigatinib for relapsed or refractory myeloid/lymphoid neoplasms with FGFR1 rearrangement. Available at: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pemigatinib-relapsed-or-refractory-myeloidlymphoid-neoplasms-fgfr1-rearrangement
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