A clinical trial led by Stanford Medicine has resulted in the FDA approval of pemigatinib, a drug aimed at treating a rare and aggressive subtype of blood cancer known as myeloid/lymphoid neoplasms (MLN) with FGFR1 gene rearrangements. This form of cancer is associated with poor survival rates, with fewer than half of patients living beyond one year.
The international Phase 2 trial involved 45 participants and showed that nearly three-quarters saw their cancers become undetectable through imaging, laboratory tests, and biopsy examinations after receiving pemigatinib. The responses lasted from months to years and allowed 13 patients to undergo potentially curative stem cell transplants.
The disease can present as either chronic or acute (blast phase) at diagnosis. Pemigatinib targets the fibroblast growth factor receptor 1 (FGFR1), which is abnormally active in this subset of MLN. Patients in the chronic phase responded most strongly to treatment, but almost half of those in the blast phase also achieved complete responses, though these were less durable.
“Essentially, everyone in the chronic phase of the disease responded well to pemigatinib treatment, and the response rate for people in the acute phase – about 44% – is still very impressive,” said Jason Gotlib, MD, professor of hematology and principal investigator for the trial. “Furthermore, the responses for people in the chronic phase are durable. I have one patient who has been on the drug for more than seven years and whose disease has not relapsed.”
At 12 months after starting treatment, estimated progression-free survival was 78%, while overall survival was 79%. At two years, these figures were 70% and 72%, respectively.
The FDA approved pemigatinib for previously treated MLN with FGFR1 rearrangements in 2022 based on these results. The study’s final outcomes were published August 26 in NEJM Evidence. Srdan Verstovsek, MD, PhD; Jean-Jacques Kiladjian, MD, PhD; and Jason Gotlib are listed as lead authors on this research.
MLN with FGFR1 rearrangement typically progresses quickly from chronic to acute phases. Median survival is under two years for chronic cases and less than a year for acute cases. Fewer than 100 such cases are diagnosed worldwide each year.
Hematopoietic stem cell transplantation remains the only potential cure but carries significant risks including graft-versus-host disease and high relapse rates after transplant—especially among those with blast-phase disease.
Researchers believe using pemigatinib before transplantation may improve success rates by reducing disease burden; its use post-transplant could help prevent relapse.
Previous tyrosine kinase inhibitors failed against MLN due to lack of specificity. “Pemigatinib is more selective,” Gotlib said. “It specifically inhibits FGFR activity.”
Pemigatinib had already received FDA approval for metastatic cholangiocarcinoma—a bile duct cancer often involving FGFR2 gene rearrangements—in 2020 after showing effectiveness against multiple FGFR family members.
“The idea for the trial started when Srdan Verstovsek treated a patient with a MLN with a FGFR1 gene rearrangement with pemigatinib, thinking that maybe it would work because it had had success in treating metastatic cholangiocarcinoma,” Gotlib said. The patient responded well, prompting further clinical investigation.
Due to MLN’s rarity, enrolling enough participants took several years after launching FIGHT-203 in 2017. Participants received oral doses of pemigatinib either intermittently or continuously; side effects like elevated phosphate levels and mouth sores were managed through dose adjustments or interruptions.
Of those enrolled with chronic-phase disease (24 patients), all but one achieved complete clinical response within six weeks; seven underwent stem cell transplantation afterward—16 maintained their response beyond one year. Among blast-phase patients (18 total), eight experienced complete responses—two lasting longer than six months—and five proceeded to transplant.
Three additional patients entered without visible disease but persistent genetic markers; all responded completely to treatment—with one going on to transplant.
“This is an extremely rare disease that is difficult to diagnose and for which few good treatment options have existed,” Gotlib said. “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. 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.”
