Real-world analysis of tyrosine kinase inhibitor treatment patterns among patients with chronic myeloid leukemia in the United States.
The treatment of chronic myeloid leukemia (CML) has improved considerably since the introduction of the tyrosine kinase inhibitor (TKI) imatinib in 2001 and the approval of second-generation TKIs (dasatinib and nilotinib) beginning in 2006.The objective of this study was to explore treatment patterns of TKI therapy (adherence, duration, and switching) among patients with CML in the United States, following the availability of second-generation TKIs.
This study used US health plan claims data from January 1, 2007, through December 31, 2011. Patients were required to be aged ≥18 years, have a prescription fill for a TKI, and a diagnosis of CML. Duration of TKI use was determined based on a gap in TKI coverage of ≥180 consecutive days after TKI initiation or switch to another TKI within the 180-day window. To account for censoring due to disenrollment from the health plan or end of the study period, median treatment duration was projected by using the Kaplan-Meier estimator.
We identified 695 patients who started TKI treatment and had a CML diagnosis during the study time frame. The mean age of patients was 55 years, and 58% of patients were male. The most common first-line TKI was imatinib (82%), with dasatinib and nilotinib use equally distributed (9%). Among the 148 (21.3%) patients who initiated a second-line TKI, the majority had switched from imatinib to dasatinib or nilotinib (86%). The median duration of first-line TKI use was 39.8 months and second-line TKI use was 22.4 months. Median duration of treatment for first-line (P = 0.4342) and second-line (P = 0.1792) treatment did not differ significantly according to TKI. Mean adherence (ie, proportion of days covered) during the first line of therapy was 0.90.
For the US patients studied, we found that imatinib was used more frequently than other TKIs in the first-line setting, but there was an increased use of second-generation TKIs in the first-line setting over time (9% in 2008 vs 43% in 2011 were nilotinib or dasatinib users). Only about one fifth of patients switched to a second-line TKI during the period of data collection.
Henk HJ
，Woloj M
，Shapiro M
，Whiteley J
... -
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Evaluation of Long-Term Chronic Myeloid Leukemia Treatment Practices with Tyrosine Kinase Inhibitors in a National Cohort of Veterans.
To evaluate nationwide chronic myeloid leukemia (CML) treatment practices over an extended period and across multiple lines of tyrosine kinase inhibitor (TKI) therapy with imatinib, dasatinib, and nilotinib.
Retrospective cohort study.
Veterans Health Administration (VHA) national database.
A total of 2873 VHA beneficiaries aged 18-89 years who had at least one encounter at any of the ~150 VHA hospitals and 800 VHA clinics, had a diagnosis code for CML, and filled at least one prescription for imatinib, nilotinib, or dasatinib between October 1, 2001, and September 30, 2010.
The VHA database was used for the time period of October 1, 2000, to September 30, 2012, allowing for a 1-year observation period to identify CML treatments prior to study enrollment and a minimum of a 2-year follow-up period to assess study end points. Primary study end points included change in TKI treatment, gaps in TKI treatment, TKI treatment persistence, and patient survival. Persistence for each distinct line of treatment was defined as the time of continuous therapy, quantified by the number of days covered by the drug from treatment initiation until a 60-day gap in treatment was identified or a switch in treatment occurred. A Kaplan-Meier model was used to evaluate persistence and survival. Of the 2873 patients receiving first-line TKI treatment, 586 (20.4%) switched to a different TKI, constituting second-line treatment. Overall, 245 patients (8.5%) were switched again to third-line treatment. Only 4.4% of patients receiving first-line treatment experienced a gap in therapy of 60 or more days. First-line treatment persistence rates were 75%, 65%, and 55% for the first, second, and third years of treatment, respectively. Five-year survival with first-line treatment was 62%.
In this national cohort of VHA patients, 1-year persistence of first-line TKI treatment was similar to that in prior studies. Five-year survival was comparable with that in other observational studies but was lower than that in prospective clinical trials. Persistence rates declined after the introduction of the new TKIs.
Kreys ED
，Frei CR
，Villarreal SM
，Bollinger MJ
，Jones X
，Koeller JM
... -
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Long-term molecular and cytogenetic response and survival outcomes with imatinib 400 mg, imatinib 800 mg, dasatinib, and nilotinib in patients with chronic-phase chronic myeloid leukaemia: retrospective analysis of patient data from five clinical trials.
Several tyrosine kinase inhibitors (TKIs) are available for treatment of patients with chronic myeloid leukaemia in chronic phase (CML-CP). We analysed long-term molecular and cytogenetic response and survival outcomes for four TKI modalities used as frontline therapy for CML-CP.
In a retrospective cohort analysis, we included data from patients with CML-CP treated in prospective clinical trials with frontline TKI modalities at a single institution between July 31, 2000, and Sept 10, 2013. The main aim of the study was to determine whether achievement of complete cytogenetic response or major molecular response had similar prognostic implications irrespective of the frontline TKI modality used. We analysed each TKI modality for response assessment and analysed survival endpoints (event-free, failure-free, transformation-free, and overall survival) with the Kaplan-Meier method. Univariate and multivariate analyses were done with Cox proportional hazard regression.
Our analysis included 482 patients who were treated with imatinib 400 mg daily (n=68), imatinib 800 mg daily (n=200), dasatinib 50 mg twice daily or 100 mg daily (n=106), or nilotinib 400 mg twice daily (n=108). More patients receiving imatinib 800 mg or second-generation TKIs (ie, dasatinib or nilotinib) achieved complete cytogenetic response (58 [87%] of 67 for imatinib 400 mg vs 180 [90%] of 199 for imatinib 800 mg, vs 100 [96%] of 104 for dasatinib vs 99 [93%] of 107 for nilotinib), major molecular response (51 [76%] vs 171 [86%] vs 93 [90%] vs 97 [91%]), and 4·5 log or higher reduction in BCR-ABL transcripts (MR(4·5) response 38 [57%] vs 148 [74%] vs 76 [71%] vs 76 [71%]). This finding was consistent over time (3-60 months). 5-year event free survival significantly differed between the imatinib 400 mg group and the other TKI groups (imatinib 800 mg p=0·029, dasatinib p=0·003, nilotinib p=0·031). There was no significant difference in 5-year failure-free survival (p=0·32, p=0·075, p=0·332), transformation-free survival (p=0·053, p=0·038, p=0·493), or overall survival (p=0·563, p=0·162, p=0·981). Multivariate analysis showed that therapy with imatinib 800 mg (HR 0·51, 95% CI 0·29-0·88, p=0·016), dasatinib (0·28, 0·12-0·66, p=0·004), or nilotinib (0·42, 0·20-0·89, p=0·024) predicted for better event-free survival compared with imatinib 400 mg, but that failure-free, transformation-free, and overall survival were similar irrespective of the TKI used. 28 (41%) patients receiving imatinib 400 mg, 85 (43%) receiving imatinib 800 mg, 23 (21%) receiving dasatinib, and 27 (25%) receiving nilotinib discontinued treatment for any reason.
Treatment with imatinib 800 mg or the second-generation TKIs dasatinib or nilotinib resulted in superior and deeper responses than did standard-dose imatinib, which were maintained after 5 years of follow-up. Results with imatinib 800 mg were similar to those with second-generation TKIs, although more patients discontinued therapy.
MD Anderson Cancer Center, National Cancer Institute.
Jain P
，Kantarjian H
，Alattar ML
，Jabbour E
，Sasaki K
，Nogueras Gonzalez G
，Dellasala S
，Pierce S
，Verstovsek S
，Wierda W
，Borthakur G
，Ravandi F
，O'Brien S
，Cortes J
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《Lancet Haematology》
ResearchGate
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