Hydroxyurea (HU) Resistance and Intolerance

ELN Consensus Criteria for Clinical Resistance and Intolerance to HU in Polycythemia Vera1

The ELN issued criteria for HU resistance and intolerance:

  • Patients are considered intolerant of or resistant to HU if even one of the criteria is met1
  • Symptoms of intolerance may also include gastrointestinal symptoms, pneumonitis, and fever at any dose of HU1
HU resistance
After 3 months of HU, at a total dose of ≥2 g/day:
  • Need for phlebotomy to maintain hematocrit levels <45% OR
  • Platelet count >400 × 109/L and WBC count >10 × 109/L OR
  • ≤50% reduction in splenomegaly or failure to completely relieve splenomegaly symptoms
HU intolerance
  • Leg ulcers or other unacceptable HU-related toxicities at any dose of HU OR
  • ANC <1.0 × 109/L or platelet count <100 × 109/L or hemoglobin <10 g/dL at the lowest dose of HU required to achieve a complete or partial response
ANC = absolute neutrophil count ELN = European LeukemiaNet HU = hydroxyurea WBC = white blood cell

PV Chart Survey

A retrospective chart review of patients with PV was conducted in the United States between April and July 2014 to investigate treatment patterns in a real-world setting.2 The study evaluated the prevalence of complete clinicohematologic response (CHR) among those currently receiving HU.3*

Included patients were ≥18 years of age who were alive within prior 6 months, had been diagnosed with PV within the past 3 to 15 years, had received HU therapy for ≥2 months in the past 5 years, had medical record data 12 months pre- and post-HU initiation, and were not a part of PV-related clinical trials.2

A total of 1,309 patient charts were reviewed by 329 hematologic oncologists, medical oncologists, and hematologists.2

Select patient characteristics included2:

  • Mean age, 62.5 years
  • Mean time since diagnosis, 5.2 years
  • 82.5% (1,080/1,309) of patients were treated with HU
    • Mean duration of HU therapy, 47 months
  • 17.5% (229/1,309) of patients discontinued HU therapy

Clinicohematologic response was defined per ELN response criteria as4:

  • Complete: Hct <45% and platelet count ≤400 × 109/L and WBC count ≤10 × 109/L and normal spleen size on imaging and no disease-related symptoms
  • Partial: In patients who do not fulfill the criteria for complete response, Hct <45% without phlebotomy or response in 3 or 4 of the 5 criteria
  • No Response: Any response that does not satisfy partial response
*Study sponsored by Incyte Corporation. Disease-related symptoms: fatigue, pruritus, or headache.
PV chart survey: Among those currently receiving HU, only 37.1% achieved a complete response based on the ELN criteria3,a
aELN response criteria are based on the following: Hct level, platelet count, WBC count, spleen size, and disease-related symptoms (microvascular disturbances, pruritus, headache).
PV chart survey: Two-thirds (66.3%) of patients receiving HU (N=1,080) had at least 1 elevated lab value3
ELN = European LeukemiaNet Hct = hematocrit HU = hydroxyurea PV = polycythemia vera WBC = white blood cell
References

1. Barosi G, Birgegard G, Finazzi G, et al. Br J Haematol. 2009;148(6):961-963. 2. Parasuraman S, DiBonaventura M, Reith K, Concialdi K. Blood. 2014;124(suppl;abstr):1852. 3. Parasuraman S, DiBonaventura M, Reith K, Concialdi K. Presented at: 56th ASH® Annual Meeting & Exposition; December 6-9, 2014; San Francisco, CA. Abstract 1852. 4. Barosi G, Birgegard G, Finazzi G, et al. Blood. 2009;113(20):4829-4833.

 
Resources
The potential impact of a target hematocrit level of <45% on major thrombosis or cardiac death.
By: MPN Connect
An animated video highlighting PV pathophysiology and mechanisms of disease.