FDA Approves Pemigatinib for Rare FGFR1-Rearranged Myeloid/Lymphoid Neoplasms Following Stanford-Led Phase II Trial
核心洞察
Nearly three-quarters of patients with FGFR1 (搜索)-rearranged myeloid/lymphoid neoplasms (搜索) achieved complete responses with pemigatinib treatment in the Stanford-led FIGHT-203 trial.
The FDA approved pemigatinib in 2022 for previously treated patients with this rare blood cancer that has a one-year survival rate of only 43%.
Treatment enabled potentially curative stem cell transplants in 13 out of 45 trial participants, offering hope for patients with limited therapeutic options.
Nearly three-quarters of patients with a rare and deadly blood cancer subtype achieved complete responses after treatment with pemigatinib in a multicenter Phase II trial led by Stanford Medicine. The dramatic results from the FIGHT-203 study prompted the FDA to approve the drug in 2022 for patients with previously treated myeloid/lymphoid neoplasms (搜索) (MLN) harboring FGFR1 (搜索) gene rearrangements.
The study, published in NEJM Evidence on August 26, enrolled 45 participants with MLN characterized by rearrangements in the fibroblast growth factor receptor 1 (FGFR1 (搜索)) gene. This subset represents a particularly aggressive form of blood cancer with a one-year overall survival rate of just 43% and fewer than 100 cases diagnosed worldwide annually.
Impressive Response Rates Across Disease Phases
Among the 24 patients with chronic phase disease, 23 achieved complete clinical responses after a median of six weeks of pemigatinib treatment. The responses proved durable, lasting at least one year in 16 of the 23 patients. Seven chronic phase patients were subsequently able to undergo stem cell transplantation.
Patients in the more advanced blast phase also showed meaningful responses, though less durable. Eight of 18 blast phase participants achieved complete responses, with five proceeding to transplantation. However, only two of these responses lasted six months or longer.
"This is an extremely rare disease that is difficult to diagnose and for which few good treatment options have existed," said Jason Gotlib, the senior author and member of the Stanford Cancer Institute. "But this drug treatment gave impressive results in patients with both chronic and acute phases of these cancers and provided a bridge to transplant for many patients."
Targeted Approach to FGFR1 Inhibition
Pemigatinib works by specifically inhibiting FGFR1 (搜索) activity, addressing the root cause of this cancer subtype. The drug belongs to a class of tyrosine kinase inhibitors but offers greater selectivity than previous attempts to treat MLN with broader-acting agents.
"Pemigatinib is more selective," Gotlib explained. "It specifically inhibits FGFR activity."
The trial concept originated when lead author Srdan Verstovsek, formerly at MD Anderson Cancer Center and now chief medical officer of Kartos Therapeutics (搜索), treated a patient with FGFR1 (搜索)-rearranged MLN using pemigatinib based on its success in treating metastatic cholangiocarcinoma (搜索), another FGFR-driven cancer.
Treatment Protocol and Safety Profile
Participants received pemigatinib as a daily oral medication, administered either continuously or in cycles of two weeks on and one week off. While side effects including elevated phosphate levels and mouth sores occurred, they were manageable through dose modifications and treatment interruptions.
The chronic phase of MLN with FGFR1 (搜索) rearrangements typically progresses to acute phase within months, with median survival under two years. Blast phase patients typically survive fewer than 12 months. The only potential cure is hematopoietic stem cell transplantation, but many patients are not healthy enough for the procedure, and relapse rates can exceed 50% in blast phase patients.
Bridging to Curative Treatment
The study's most significant finding may be pemigatinib's ability to serve as a bridge to potentially curative stem cell transplantation. By reducing disease burden prior to transplant, the treatment could improve transplant success rates. Additionally, post-transplant use may help prevent relapse.
The FIGHT-203 trial, funded by Incyte Corporation, launched in 2017 and took several years to complete enrollment due to the disease's rarity. Incyte markets pemigatinib under the trade name Pemazyre, which received FDA approval for metastatic cholangiocarcinomas in 2020 before its approval for MLN in 2022.
"It's another example of targeted therapy giving patients who otherwise have little hope a chance for extended survival and an improved quality of life," Gotlib noted.