Cost of Myelosuppression with the Second Generation Tyrosine Kinase Inhibitors (TKIs) in Imatinib Resistant/Intolerant Chronic Myelogenous Leukemia (CML): An Economic Analysis Using Global Literature.
Bibliographic record
Abstract
Abstract Background: New targeted therapies such as nilotinib and dasatinib show promise as options for patients with imatinib-resistant or -intolerant CML; however, concerns exist for these agents related to myelosuppression. The objective of this study was to compare the short-term cost of myelosuppression, from a global perspective, for chronic and accelerated phase CML patients treated with nilotinib and dasatinib. Methods: A global systematic literature review of the past 10 years was conducted using MEDLINE, Econlit and EMBASE to examine the potential costs of myelosuppression (specifically anemia, neutropenia and thrombocytopenia) in adult cancer patients, from the perspective of a health-care payer. An economic analysis was then developed using the ranges of cost data reported in literature, as well as the incidence rates of Grade 3/4 anemia, neutropenia and thrombocytopenia from nilotinib phase II clinical study reports and the dasatinib package insert for chronic and accelerated phase CML. All costs/currencies were converted to US dollars and inflated to 2006 using the country-specific medical inflation rates. Results: The cost of managing myelosuppression varied widely among countries based on patterns of inpatient compared to outpatient treatment, as well as the use of transfusions compared to recombinant growth factors. The reported cost ranges per AE episode were $124–$12,646 for anemia, $300–$27,440 for neutropenia and $239–$12,223 for thrombocytopenia from the following countries: UK, France, Germany, Italy, Spain, Netherlands, Finland, Switzerland, Belgium, Canada and the US. Expected 6-month costs per patient for Grade 3/4 myelosuppression adverse events with nilotinib and dasatinib are shown as ranges below: Chronic Phase Accelerated Phase Nilotinib $238–$5,550 $394–$9,064 Dasatinib $415–$9,929 $1,155–$23,674 Conclusions: Reflecting a broad range of countries, the expected short-term costs of Grade 3/4 myelosuppression with dasatinib may be 1.7 to 2.9 times higher than that associated with nilotinib. When considering the economic implications of different treatment options for imatinib-resistant or -intolerant CML, both the cost of the drug and the cost of managing adverse events should be taken into account. Future observational studies should be conducted to prospectively assess real-world adverse event costs with the second generation TKIs.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.008 | 0.019 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.010 |
| Bibliometrics | 0.018 | 0.021 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.002 | 0.002 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".