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Monitoring Response to TKI Therapy by PCR Improves Outcomes in Chronic Myeloid Leukemia

TOP - May 2015, Vol 8, No 2

Disease progression is slower and overall survival (OS) is greater in patients with chronic myeloid leukemia (CML) who are being monitored for their response to tyrosine kinase inhibitor (TKI) therapy and show good adherence. However, few clinicians monitor response and adherence to oral TKI treatment in patients with CML.

Data from 245 patients with newly diagnosed chronic-phase CML cared for in the Southern California Permanente Medical Group show that although most patients start TKI therapy within 90 days of diagnosis, only approximately 66% show high adherence to therapy, and using polymerase chain reaction (PCR) monitoring to evaluate response to treatment can improve outcomes.

“We found that patients who had any monitoring by PCR had better outcomes than those who did not undergo monitoring, and this was independent of their insurance level,” said Reina Haque, PhD, MPH, Cancer Epidemiologist and Research Scientist II, Kaiser Permanente, Pasadena, CA. “To avoid bad outcomes, patients must be monitored.”

Dr Haque and colleagues collected data from electronic health records and chart reviews, including TKI use and adherence, healthcare utilization, and clinical outcomes. Adherence to TKI therapy was measured by medication possession ratio (MPR), the number of days a medication is supplied divided by the number of days between the first and last drug dispensing date. Patients were classified into good adherence (MPR ≥90%) and poor adherence (MPR <90%). The mean MPR for TKI use was 88%.

More than 90% of the cohort started TKI therapy within 3 months of diagnosis. Virtually all patients (96%) began therapy with imatinib (Gleevec). Despite full pharmacy coverage, only 63% of patients showed good adherence. The reasons for first-line treatment discontinuation included:

  • Adverse effects: 41 patients
  • Incomplete cytogenetic or molecular response: 38 patients
  • Drug nonresponse, provider recommendation, or nonadherence: 21 patients
  • Bone marrow/stem-cell transplant: 7 patients.

Disease progression and OS were evaluated in patients diagnosed in 2001-2006 who received imatinib. With a mean follow-up of 5.1 years (maximum, 13 years), the rate of chronic-phase CML progression to accelerated phase or blast crisis phase was lower in patients with good adherence (10.0 per 1000 person-years) than in those with poor adherence (14.2 per 1000 person-years).

Patients with high adherence had a lower mortality rate than those with low adherence (25.9 per 1000 vs 39.2 per 1000 person-years). OS was better in patients with high adherence, although the difference did not achieve significance.

PCR Monitoring and Outcomes

The key to outcomes, however, was PCR monitoring. “We found that patients who underwent PCR monitoring had a significantly reduced risk of a composite outcome of progression, bone marrow or stem-cell transplant, or mortality, regardless of their TKI adherence status, whereas MPR was not associated with the outcomes,” said Dr Haque.

Specifically, the hazard ratio for the composite outcome was 0.6 with PCR monitoring in patients with MPR ≥90% and 0.10 in patients with MPR <90%.

Education Intervention Persuades Clinicians

In a separate study, an educational intervention was successful in persuading healthcare professionals to discuss the impact of nonadherence to TKI on CML outcomes.

Sara R. Fagerlie, PhD, Director of Scientific Services at Educational Concepts Group in Atlanta, measured the impact of 1-hour educational interventions that addressed frontline treatment and treatment for relapse of CML. The programs educated 631 providers in the community setting. Participants were asked about communication and follow-up with patients with CML before and after the intervention.

Before the education, “more than half were not evaluating adherence for a CML patient who missed major response milestones,” said Dr Fagerlie, and only 60% reported always discussing the impact of TKI nonadherence on clinical outcomes in CML.

“With just the 1-hour intervention, practitioners were recognizing when they needed to evaluate adherence, and 86% were planning to discuss the impact of adherence with their patients,” Dr Fagerlie said. Education also resulted in a 13% increase in providers incorporating technology, such as texting, e-mail, or cell phone application as a patient adherence tool.

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