Imatinib mesylate has been a standard first-line treatment for newly diagnosed chronic phase chronic myeloid leukemia (CP-CML) patients at a recommended initial dose of 400mg. Dose escalation of imatinib has been shown to overcome imatinib resistance in some patients; however, recent National Comprehensive Cancer Network (NCCN) guidelines recommend switching to second generation tyrosine kinase inhibitors (TKIs) for imatinib resistant or intolerant CP-CML patients. Limited evidence exists regarding the real-world treatment patterns among CP-CML patients initiating treatment with imatinib. Thus, the objectives of the study were to evaluate treatment patterns including dosing patterns and reasons for dose modification; rates of treatment interruption (i.e., drug holiday), discontinuation, and switching to second generation TKIs; and investigate the reasons for treatment interruption, and discontinuation among newly diagnosed CP-CML patients initiating treatment with imatinib in the real-world setting.
We conducted a retrospective study utilizing the Georgia Cancer Specialist (GCS) electronic medical record system. CP-CML patients initiating treatment with imatinib from 01-01-2002 to 11-01-2011 were identified. Patients in clinical trials, diagnosis with accelerated/blast crisis, having less than 6-month follow-up time or receiving concurrent treatment for other primary cancers were excluded. Data on imatinib dosing, rates of treatment interruption, discontinuation defined as patients with no record of resuming imatinib treatment, switching, with corresponding reasons for the observed patterns were extracted through comprehensive chart reviews and summarized using standard descriptive statistics.
A total of 177 patients with CP-CML initiating treatment with imatinib between 01-01-2002 and 11-01-2011 met study inclusion criteria. The median duration of treatment with imatinib was 35 months. The average age of patients treated with imatinib was 61 years and the majority (n = 144, 81%) had a good (0–1) Eastern Cooperative Oncology Group (ECOG) performance status score. Hypertension (n = 52, 29%) was the most common comorbidity in this cohort followed by diabetes mellitus (n = 17, 9.6%). Dose modification was noted for 33% (n = 59) of the patients. The initial dose for patients with a dose modification was 400 mg for the majority (n = 55, 93%) of patients. Major reasons for dose modification among the 59 patients with dose modification included lack of efficacy as documented in the physician notes (n = 20, 34%), leading to a dose increase for all 20 patients, and intolerance (n = 23, 39%), leading to a dose reduction in more than half of the patients who did not tolerate imatinib (n = 13, 56%). Rates of treatment interruption, discontinuation and switching to another therapy were 16% (n = 29), 24% (n = 43), and 23% (n = 41), respectively. The major reason for treatment interruption among the 29 patients with treatment interruption was intolerance (n = 15, 52%) due to side effects such as rash, pancytopenia and myalgia. Primary reasons for treatment discontinuation among the 43 patients discontinuing imatinib treatment included lack of efficacy (n = 27, 63%) and intolerance to imatinib (n = 13, 30%). Of the 27 patients discontinuing imatinib treatment due to lack of efficacy, 9 patients (33%) had an initial dose escalation to 600mg or 800 mg and most patients (n = 26, 96%) eventually switched to a second generation TKI. Among the 41 patients who switched therapies, 23 (56%) switched to dasatinib while 18 (44%) switched to nilotinib over a median time of 14 months (range: 1.3 – 94.9 months).
This retrospective review of patients with CP-CML receiving imatinib in a community outpatient setting found that almost a quarter to one-third of patients initiating treatment with imatinib experienced changes in treatment that included dose modification, treatment interruption, or discontinuation. These changes were primarily due to lack of efficacy or intolerance. Although imatinib is highly effective and generally well tolerated as a first-line treatment for CP-CML, alternative and more effective second generation TKIs could be considered as first-line therapy, or alternative to high dose imatinib among those who are resistant to imatinib.
Sail:Novartis: Received funding from Novartis for research study Other. Chen:Novartis Oncology: Employment, Own stock in Novartis Other. Jackson:Novartis: Received funding from Novartis for research study Other. Ericson:Novartis Pharmaceuticals Corp: Employment, Equity Ownership.
Asterisk with author names denotes non-ASH members.