Monitoring treatment response to tyrosine kinase inhibitor (TKI) therapy is critical in the management of patients with chronic myeloid leukemia (CML) to assess suboptimal response and detect resistance. This study aimed to evaluate the monitoring patterns and treatment response of CML patients treated with imatinib in a community setting.
A retrospective study was conducted utilizing the Georgia Cancer Specialist (GCS) electronic medical record system. Patients with Ph+ chronic phase CML (CP-CML) initiating imatinib from 01-01-2002 to 11-01-2011 were included, while patients in clinical trials, with <6 months follow-up, or receiving concurrent treatment for other primary cancers were excluded. Imatinib response monitoring frequency and corresponding outcomes were collected by a medical chart review. Treatment responses were defined at time points consistent with European LeukemiaNet (ELN) and National Comprehensive Care Network (NCCN) guidelines, including partial cytogenetic response, PCyR (1% to 35% Ph+ metaphases); complete cytogenetic response, CCyR (no Ph+ metaphases); major molecular response, MMR (≥3.0 log reduction of BCR-ABL mRNA); and complete molecular response, CMR (undetectable BCR-ABL mRNA). In addition, proportion of patients with failure/sub-optimal response and their subsequent frequency of monitoring were also assessed. Data were summarized using descriptive statistics.
A total of 177 patients, with a mean age of 61 years, met study criteria. The median duration of imatinib treatment was 35 months. The majority of patients (n = 144, 81%) had an ECOG score of 0–1. Among patients on therapy during the first 3 months (n = 168), most patients (n = 165, 98%) had a hematologic test as recommended by guidelines. The proportion of patients who had a cytogenetic test performed decreased over time for those on imatinib treatment who had not achieved CCyR, from 29% at 3 months to 17% at 18 months. Molecular monitoring frequency varied from 51% at 3 months to 56% at 18 months among those patients that were tested. Among patients who were monitored at least once for cytogenetic response within 18 months of initiating treatment with imatinib (n = 96), 50 patients had documented evidence of achieving CCyR. Among patients who were monitored at least once for molecular response within 18 months of initiating treatment with imatinib (n = 140), 37 patients had documented evidence of achieving MMR or CMR. Among the 37 patients achieving a CMR or MMR within 18 months, 21 (60%) had a subsequent molecular monitoring test within 6 months. Among 73 patients not achieving CMR or MMR by 18 months, there was a follow-up molecular monitoring test within 6 months for 53 (70%) patients. Additionally, patients who were regularly monitored for molecular response (n = 38) within the first 12 months of imatinib initiation did not have any indication of progressive disease, compared to 12% (n = 17) with progression among patients not regularly monitored within first 12 months of initiating imatinib (n = 139).
This retrospective review of patients with Ph+ CML receiving imatinib in a community outpatient setting found that there is considerable under-monitoring of treatment response. This may result in under-detection of patients with treatment resistance or suboptimal response which limits the ability to modify or switch TKI treatment accordingly, and ultimately compromises patient outcomes. Results also suggest that compliance to monitoring guidelines may be associated with better clinical outcomes among patients that may experience early resistance to imatinib. Possible limitations of this study may include missing data (e.g., omission of tests or testing results) due to retrospective nature of the chart review.
Jackson:Novartis: Received funding from Novartis for research study Other. Chen:Novartis Oncology: Employment, Own stock in Novartis Other. Sail:Novartis: Received funding from Novartis for research study Other. Ericson:Novartis Pharmaceuticals Corp: Employment, Equity Ownership.
Asterisk with author names denotes non-ASH members.