How is leukopenia (low white blood cell count) managed in patients taking futibatinib (a fibroblast growth factor receptor inhibitor)?

Management of Leukopenia in Patients Taking Futibatinib

For patients taking futibatinib who develop leukopenia, treatment should be temporarily interrupted until white blood cell counts recover to acceptable levels, followed by dose reduction if necessary.

Understanding Leukopenia with FGFR Inhibitors

Leukopenia (low white blood cell count) is a recognized hematologic adverse effect that can occur with fibroblast growth factor receptor (FGFR) inhibitors like futibatinib. While hyperphosphatemia is the most common adverse event with futibatinib, hematologic toxicities including leukopenia require careful monitoring and management.

Monitoring Recommendations

• Initial monitoring: Complete blood counts should be checked weekly during the first 4-6 weeks of treatment 1
• Subsequent monitoring: Every 2 weeks or monthly until month 3, depending on blood count stability 1
• Long-term monitoring: Every 3 months after the initial 3-month period 1
• More frequent monitoring is advised for patients with advanced disease 1

Management Algorithm for Leukopenia

Step 1: Assessment

• Determine severity of leukopenia (grade)
• Check if leukopenia is related to underlying disease or medication

Step 2: Management Based on Severity

For neutropenia (which is often the most clinically significant component of leukopenia):

1. Grade 3-4 neutropenia (ANC < 500/mm³):

   • Hold futibatinib until ANC ≥ 1000/mm³ 1
   • If recovery occurs within 7 days: Resume at original starting dose
   • If ANC < 500/mm³ for more than 7 days: Reduce by one dose level

2. For persistent leukopenia:

   • Check if leukopenia is related to underlying malignancy (bone marrow aspiration or biopsy may be needed) 1
   • If unrelated to malignancy and persists > 2 weeks: Consider dose reduction
   • If persists > 4 weeks: Consider temporary discontinuation until recovery

Step 3: Supportive Measures

• Growth factors (G-CSF) can be used in combination with futibatinib for patients with resistant neutropenia 1
• Monitor for signs of infection while neutropenic

Important Considerations

• Risk of infection: Patients with neutropenia are at increased risk of infection. Deaths due to infection have been reported with other TKIs, though at relatively low rates 1

• Bleeding risk: If leukopenia is accompanied by thrombocytopenia, be aware that some FGFR inhibitors may also affect platelet function, increasing bleeding risk 1

• Monitoring for recovery: After dose interruption, ensure adequate recovery of white blood cell counts before resuming treatment

• Long-term effects: The long-term consequences of cytopenias with FGFR inhibitors are not well established, but with other TKIs, neutropenia during the first 3 months of therapy has been associated with lower progression-free survival 1

Futibatinib-Specific Information

In clinical trials of futibatinib:

• The recommended phase II dose was determined to be 20 mg once daily 2, 3
• Most common adverse events were hyperphosphatemia (59-100%), diarrhea (37%), and constipation (34%) 2, 3
• Treatment-emergent adverse events led to dose interruptions in 55% of patients 2
• Dose reductions were required in 14% of patients 2
• Only 3% of patients discontinued treatment due to adverse events 2

Pitfalls to Avoid

• Delayed recognition: Regular monitoring is essential as leukopenia may develop at any time during treatment
• Underestimating severity: Even mild leukopenia should be taken seriously and monitored closely
• Overlooking drug interactions: Consider if other medications might be contributing to leukopenia
• Failure to distinguish disease-related vs. drug-induced cytopenias: Especially important in patients with advanced disease

By following these guidelines, leukopenia in patients taking futibatinib can be effectively managed while maximizing the therapeutic benefit of this targeted therapy.