Original Contribution Study of Imatinib Treatment Patterns and Outcomes Among US Veteran Patients With Philadelphia Chromosome–Positive Chronic Myeloid Leukemia By Nancy Vander Velde, MD, Lei Chen, MD, PhD, Amy Guo, PhD, Hari Sharma, Maryna Marynchenko, MBA, Eric Q. Wu, PhD, Jinan Liu, PhD, Heidi Yang, MPH, and Lizheng Shi, PhD Tulane University; Southeast Louisiana Veterans Health Care System, New Orleans, LA; Novartis Pharmaceuticals Corporation, East Hanover, NJ; and Analysis Group, Boston, MA Abstract Purpose: This study investigated the treatment patterns and outcomes for US veteran patients with chronic myeloid leuke- mia– chronic phase (CML-CP) initiated on imatinib (IM). Patients and Methods: Patients (age 18 years) with at least one CML diagnosis (International Classification of Dis- eases, Ninth Edition Clinical Modification: 205.1x) during the period January 1, 2000, to June 30, 2011, and initiated on IM as first-line therapy were identified in the VISN 16 data ware- house (N = 137). Accelerated and blastic phases (AP/BP) were identified on the basis of WHO classification using complete blood count (CBC) data. Rates of IM dose adjust- ment, discontinuation, and switching to another drug therapy were estimated. Time to discontinuation, progression to AP/ BP, and survival were assessed using Kaplan-Meier analy- sis (KM). Results: During follow-up, 19.0% of patients had at least one dose increase; of these, 19.2% switched to another therapy. Dose reductions occurred in 25.6% of patients. Among patients who discontinued IM (n = 74; 54.0%), whereas 16.2% switched to other therapies, 27.0% neither restarted IM nor switched to other thera- pies. KM showed that 25.6% and 42.4% of patients discontinued IM treatment by year 1 and 2, and 8.1% and 16.0% demonstrated disease progression by year 1 and 2, respectively. Among patients who experienced disease progression (n = 28), 32.1% continued IM postprogression, 32.1% discontinued IM before progression, 28.6% discontinued IM postprogression without switching, and 7.1% switched to other therapies postprogression. The mortality rates were 3.0% and 9.5% after IM initiation, and 21.7% and 42.7% after disease progression by year 1 and 2, respectively. Conclusion: In this veteran population, a substantial number of IM-treated patients, including those with disease progression, either discontinued or interrupted IM use without switching to other therapies. Introduction Chronic myeloid leukemia (CML) is a hematopoietic stem-cell disease resulting from DNA damage, and leading to the forma- tion of the fusion gene BCR-ABL, which encodes a constitu- tively active tyrosine kinase. 1,2 CML accounts for 11.3% of all new leukemia cases, 3 with an annual incidence of approxi- mately 4,800 cases in the United States alone. 3,4 The disease is usually diagnosed during a prolonged chronic phase in which most patients experience mild symptoms of fatigue, anorexia, and weight loss 2 ; overall survival rates from diagnosis of CML have been reported at 80% to 85% in 7- to 10-year periods. 5 Patients may, however, eventually progress to an accelerated phase characterized by rising numbers of poorly differentiated cells in the peripheral blood and bone marrow, a phase that can last for approximately 6 months before advancing to a rapidly fatal blastic phase. 6 Therapeutic options for CML vary according to disease phase, prior treatment history and outcomes, and other prog- nostic factors. Imatinib (IM), the prototype BCR-ABL tyrosine kinase inhibitor (TKI), received FDA approval in 2001 and has largely replaced conventional drug therapy (eg, interferon-alfa and hydroxyurea) as the first-line therapy for newly diagnosed CML chronic phase (CML-CP). The standard starting dose of IM for the chronic phase is 400 mg daily, with a recommended reduction to 300 mg in the event of toxicity. 7 IM induces com- plete cytogenetic response in a majority of newly diagnosed patients, 8 and has vastly improved survival in CML. 4 However, a subset of patients exhibit poor response or experience relapse despite standard-dose IM treatment. 9,10 Resistance to IM can occur as a result of amplification or mutation of the BCR-ABL gene, or through other mechanisms independent of BCR- ABL. 11 Dose escalation to 600 mg or 800 mg is considered one acceptable approach in this setting, though the observed bene- fits of dose increase have varied substantially. 7,10 Alternative options include switching to nilotinib or dasat- inib, more potent second-generation TKIs, which have since been approved for newly diagnosed and IM-resistant or -intol- erant CML. Although no improvement in overall survival com- pared with imatinib has been demonstrated in clinical trials, treatments with nilotinib or dasatinib are associated with higher rates of achieving major molecular responses (defined as 3 log reduction in BCR-ABL transcript level based on the Interna- tional Scale). 12,13 In addition, fewer patients treated with nilo- tinib experienced progression to accelerated or blastic phase (AP/BP) when compared with patients treated with imatinib. 13 Nilotinib and dasatinib are active against many IM-resistant mutations of the BCR-ABL kinase domain, 14 have demon- strated superior efficacy to IM as first-line therapies in the Health Care Delivery e212 J OURNAL OF O NCOLOGY P RACTICE • V OL . 9, I SSUE 5 Copyright © 2013 by American Society of Clinical Oncology Downloaded from ascopubs.org by 54.81.122.103 on June 19, 2022 from 054.081.122.103 Copyright © 2022 American Society of Clinical Oncology. All rights reserved.