Understanding United States (US) Treatment Practices for the Management of Chronic Myeloid Leukemia (CML) in Clinical Practice: A US Subgroup Analysis of the WORLD CML Registry.

The WORLD CML Registry, with sites in the US, Latin America, Asia-Pacific, the Middle East, Africa, Russia, and Turkey, is a multinational, prospective registry established to longitudinally assess global clinical practice patterns for the management of patients (pts) with CML. Here, we report updated results for the subgroup of pts at US sites and evaluate alignment of US practice patterns with current National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines for CML (http://www.nccn.org).

Pts (≥ 16 y of age) within 6 mo + 2 weeks of confirmed CML diagnosis were enrolled. Baseline demographics and medical history were collected at enrollment. Information on disease status and management was collected approximately every 6 mo or with a change in disease status or management. Adverse events (AEs) were collected only if they resulted in a dose/regimen change, nonadherence to treatment, or death.

This analysis includes 377 evaluable pts (those with confirmed informed consent forms and no protocol deviations) of 418 total pts enrolled in the US from February 2008 to December 31, 2010. Median age was 53 y (range, 18–91 y), with 26% ≥ 65 y of age. CML diagnosis was confirmed using hematologic (85%), bone marrow (84%), cytogenetic (82%), and molecular (polymerase chain reaction [PCR]; 52%) assessments. Nearly all pts (96%) were diagnosed in chronic phase (CP; Table). Most pts with CML-CP (73%) were treated with imatinib (Glivec^®/Gleevec^®) as first-line therapy (additional pts may have received first-line imatinib in a clinical trial). Median duration of imatinib treatment in CML-CP pts was 7.59 mo (range, 0.03–33.54 mo). In CML-CP pts (n = 363), imatinib dose was increased in 29 pts (8%; primary reasons included physician request [4%] and lack of efficacy [7%]), decreased in 32 pts (9%; primary reasons included AEs [5%] and physician request [3%]), and interrupted in 10 pts (3%; primary reasons included AEs [2%]). Regimen was switched from imatinib to nilotinib in 21 pts (6%; primary reasons included lack of efficacy [2%] and AEs [2%]) and to dasatinib in 20 pts (6%; primary reasons included AEs [2%], lack of efficacy [1%], and physician request [1%]). Disease burden over time on imatinib was most commonly assessed using blood counts (Table). Only 16% of pts had a molecular assessment at 3 mo; at later time points, 43%-64% of pts had molecular assessments. Cytogenetics was least common (done in 13% of pts at 3 mo and 25%-34% of pts at later time points). AEs reported in ≥ 1% of all pts in the analysis were nausea (3%), fatigue (2%), rash (2%), diarrhea (2%), headache (2%), thrombocytopenia (2%), neutropenia (1%), and dyspnea (1%). There were 17 deaths (5%) reported; 5 deaths were related to CML progression, 1 was related to CML treatment (necrotizing pneumonia), 7 were unrelated to CML treatment, and 4 had unknown causes.

In the US, many pts treated with first-line imatinib did not have routine molecular or cytogenetic assessments, suggesting that many US physicians do not monitor their patients as recommended by the NCCN guidelines. These findings may reflect the lack of readily available molecular testing during part of the time period evaluated by this registry.

Hermann:Novartis: Sponsor -paid expenses of reported trial Other. Miller:Novartis: Consultancy, Research Funding, Speakers Bureau, development of educational presentations Other; Incyte: development of educational presentations, development of educational presentations Other. Snyder:Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees. Ericson:Novartis Pharmaceuticals Corp: Employment, Equity Ownership. Zernovak:Novartis Pharmaceuticals Corp: Employment, Equity Ownership. Juma:Novartis Pharmaceuticals Corp: Employment. Cortes:Novartis: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Ariad: Consultancy, Research Funding.