- The prognosis for patients with myeloid/lymphoid neoplasms with FGFR1 rearrangements is poor, and treatment options are limited.
- In a phase II study of these patients, the overall complete response rate with the FGFR1-3 inhibitor pemigatinib was 74%.
- For patients with chronic-phase disease, the complete response rate was 96%.
Most patients with myeloid/lymphoid neoplasms with FGFR1 rearrangements receiving pemigatinib (Pemazyre) experienced complete responses in the phase II FIGHT-203 trial.
Among 45 patients analyzed for efficacy, the overall complete response rate was 74% with the oral FGFR1-3 inhibitor, with responses of 96% in those in chronic phase and 44% in those in blast phase, reported Jason Gotlib, MD, of Stanford Cancer Institute and Stanford University School of Medicine in California, and colleagues.
A complete cytogenetic response occurred in 73% of patients overall -- 88% of those in chronic phase, 50% of those in blast phase, and in all three patients who had a rearrangement only, they noted in NEJM Evidence.
This study "demonstrated encouraging treatment responses for patients with chronic-phase disease who were ineligible for transplantation and may facilitate bridging to transplantation in both early and advanced disease," Gotlib and team concluded.
The prognosis for myeloid/lymphoid neoplasms with FGFR1 rearrangements is poor, with a reported 1-year overall survival (OS) rate of 43%, and treatment options are limited. Pemigatinib was approved by the FDA in 2022 for relapsed or refractory myeloid/lymphoid neoplasms with FGFR1 rearrangements, based on interim data from FIGHT-203.
In an editorial accompanying the study, Vivian G. Oehler, MD, and Roland B. Walter, MD, PhD, both of the Fred Hutchinson Cancer Center in Seattle, wrote that though FIGHT-203 was an uncontrolled study, "with inherent selection biases," the results substantiated the efficacy and tolerability of pemigatinib in this patient population, and provided "a rationale for its combination with other agents in blast-phase patients."
However, they noted that the study leaves several questions unanswered.
For example, they observed that pemigatinib's efficacy in chronic-phase disease "raises the question of whether a subset of such patients could defer or avoid hematopoietic cell transplantation."
"Long-term outcomes may address this question, but few patients have received therapy for more than 4 years," they pointed out.
They also noted that while a complete cytogenetic response is associated with survival in chronic myeloid leukemia, it is unclear how the depth of therapeutic response affects the durability of remission or survival in this patient population.
For this study, Gotlib and team recruited patients from April 2017 through April 2022 at 21 sites in the U.S., Europe, Canada, and Japan. Eligible patients had relapsed after hematopoietic cell transplantation or another prior therapy, or were not current candidates for transplantation or other therapies.
Patients received oral pemigatinib 13.5 mg once daily on an intermittent (2 weeks on, 1 week off) schedule, which was ultimately changed to a continuous schedule.
The efficacy population of 45 patients had a median age of 61 years, and 56% were women. Of these patients, 53% were in the chronic phase of illness, 40% were in blast phase, and three previously treated patients exhibited the rearrangement without morphologic bone marrow or extramedullary involvement.
The median time to complete response was 1.5 months, and the median duration of complete response was not reached. Complete responses were maintained for 12 months or longer in 70% of patients with chronic-phase disease, while 25% with blast-phase disease had complete responses lasting 6 or more months.
Median progression-free survival (PFS) was 73.9 months, and median OS was not reached. At 12 and 24 months, respectively, estimated PFS rates were 78% and 70%, and OS rates were 79% and 72%.
Hematologic treatment-emergent adverse events (TEAEs) occurred in 45% of patients, with anemia being the most frequent. Non-hematologic TEAEs occurred in all patients, the most common of which was hyperphosphatemia (76%). The most common ≥grade 3 event was stomatitis (19%).
Treatment discontinuations, interruptions, and dose reductions occurred in 11%, 64%, and 60% patients, respectively.
"Future studies with longer follow-up are needed to determine whether depth of molecular responses correlates with duration of clinical response, as well as with progression-free and overall survival," Gotlib and colleagues noted.
Disclosures
The study was funded by Incyte.
Gotlib reported relationships with Blueprint Medicines, Cogent Biosciences, Incyte, and Protagonist Therapeutics.
Co-authors reported multiple relationships with industry, including Incyte.
Oehler reported relationships with Novartis, Ascentage Pharma, Terns Pharmaceuticals, and Takeda. Walter reported no conflicts of interest.
