Identifying and Managing Treatment Failure: Resistance and Intolerance Criteria
Panelists discuss how in polycythemia vera (PV), defining and managing treatment resistance or intolerance is crucial, requiring careful monitoring and timely intervention, including assessing adherence, evaluating mutations, and making therapeutic adjustments such as dose modifications, switching to alternative therapies like ruxolitinib or interferon, and employing a multidisciplinary approach to ensure optimal disease control and patient outcomes.
Summary for Physicians: Defining and Managing Treatment Resistance or Intolerance in PV
In polycythemia vera (PV), treatment resistance or intolerance is a critical issue that requires careful monitoring and timely intervention. Suboptimal responses to initial therapeutic strategies necessitate a thorough evaluation to guide adjustments in treatment and ensure optimal disease control.
Defining Treatment Resistance or Intolerance:
- Resistance is characterized by inadequate or insufficient response to therapy, such as:
- Failure to maintain hematocrit control despite optimal phlebotomy and cytoreductive therapy
- Persistent or rising blood counts (eg, leukocytosis, thrombocytosis) despite adherence to treatment
- Worsening symptoms (eg, pruritus, fatigue, splenomegaly) despite therapy
- Intolerance is defined by the inability to tolerate the adverse effects of a treatment, which can include:
- Myelosuppression (eg, anemia, thrombocytopenia)
- Gastrointestinal distress, liver toxicity, or other significant adverse events
Managing Suboptimal Responses:
- Assessment:
- Confirm adherence to therapy and exclude secondary causes for lack of response (eg, infection, new comorbidities).
- Assess for mutations that may affect response to specific therapies, such as JAK2 or other driver mutations.
- Consider dose adjustments or switching treatment based on the severity of adverse effects or disease progression.
- Therapeutic Adjustments:
- For Resistance: If a patient is not responding to hydroxyurea (HU), consider increasing the HU dose, switching to a more potent therapy like ruxolitinib (for splenomegaly or symptom burden), or introducing interferon as an alternative.
- For Intolerance: For patients intolerant to HU, alternatives like pegylated interferon or ruxolitinib (if indicated) may be used. If ruxolitinib is not suitable, consider adjusting the dose or switching to a different cytoreductive agent.
- Multidisciplinary Approach:
In cases of severe or complex resistance, a multidisciplinary team (including hematologists, specialists in supportive care, and pharmacists) may be needed to optimize management and improve outcomes.
Conclusion: Identifying resistance or intolerance early and adjusting therapy appropriately is essential for maintaining long-term control in PV. Regular monitoring of clinical and laboratory parameters is critical for detecting suboptimal responses and guiding treatment decisions.
