4  FGFR1 rearrangements

4.1 Pemigatinib

4.1.1 Pemigatinib for Myeloid/Lymphoid Neoplasms with FGFR1 Rearrangement (FIGHT-203 Trial)(Verstovsek et al. 2025)

Key Trial Findings:

Efficacy by Disease Phase:

  • Chronic phase: Exceptional response with 96% complete response rate (23/24 patients)
  • Blast phase: Moderate response with 44% complete response rate (8/18 patients)
  • Overall: 74% complete response rate across all patients

Response Durability:

  • Median duration of complete response was not reached (95% CI: 27.9 months to NR)
  • 70% of chronic-phase patients maintained response ≥12 months
  • Only 25% of blast-phase patients maintained response ≥12 months
  • This stark difference highlights the importance of early treatment

Survival Outcomes:

  • Median PFS: 73.9 months (95% CI: 29.2 to NR)
  • Median OS: Not reached
  • 12-month survival rates: 78% PFS, 79% OS
  • 24-month survival rates: 70% PFS, 72% OS

Clinical Impact:

  • 29% of patients (13/45) successfully bridged to allogeneic hematopoietic cell transplantation
  • Particularly notable: 30% of chronic-phase complete responders bridged to transplant
  • Only 1 patient (4%) with chronic-phase disease progressed to blast phase during treatment

Safety Considerations:

  • Most common AE: Hyperphosphatemia (77% any grade, 4% grade ≥3)
  • Most common grade ≥3 AE: Stomatitis (21%)
  • 60% required dose reductions, 64% dose interruptions
  • Only 9% discontinued due to adverse events
  • Continuous dosing showed better efficacy than intermittent dosing despite higher toxicity management needs