Patient adherence to tyrosine kinase inhibitor therapy in chronic myeloid leukemia.

Dramatically improved survival associated with tyrosine kinase inhibitor (TKI) therapy has transformed the disease model for chronic myeloid leukemia (CML) to one of long-term management, but treatment success is challenged with poor medication adherence. Many risk factors associated with poor adherence can be ameliorated by close monitoring, dose modification, and supportive care. Controlling risk factors for poor adherence in combination with patient education that includes direct communication between the health care team and the patient are essential components for maximizing the benefits of TKI therapy.

CML treatment in Asia-Pacific region.

CML in Asia seems to affect the younger age group and more patients are in the high and intermediate Sokal risk group. Cytogenetic study and molecular testing are done mostly at diagnosis, but monitoring the response is limited due to the cost and accessibility. The treatment of chronic phase CML has changed dramatically within the last decade and imatinib has become the standard treatment for CP, CML. Since the cost of imatinib is quite high, most Asian patients cannot afford it. Patients in several countries get imatinib through Glivec International Patient Assistant Program. Patients who are intolerant or resistant to imatinib usually get the second generation tyrosine kinase inhibitors (TKIs), either nilotinib or dasatinib. The National Health Insurance covers all or most of the cost of imatinib in South Korea, Hong Kong and Taiwan. Both nilotinib and dasatinib are partially or fully covered by national insurance in Australia, Japan, Singapore and Taiwan as the second-line therapy. TKIs treatment remains out of reach for many Asian CML patients, especially those in the rural areas and those who are not eligible for patient access programs or covered by the national insurance. The cytogenetic response to imatinib in Asian CML patients varies considerably, from as low as 24% to as high as 96%. The Asia CML Study Alliance was briefly presented.

Cost-effectiveness of dasatinib and nilotinib for imatinib-resistant or -intolerant chronic phase chronic myeloid leukemia.

OBJECTIVES: To estimate the cost-effectiveness of dasatinib and nilotinib compared with high-dose imatinib for people with chronic phase chronic myeloid leukemia, which are resistant to normal-dose imatinib and compared with interferon-α for people intolerant to imatinib, from the perspective of the UK National Health Service. METHODS: An an area under the curve partitioned survival model was developed to estimate the cost-effectiveness of dasatinib and nilotinib. Clinical effectiveness evidence was taken mostly from single-arm trials. RESULTS: Both progression-free survival and overall survival are highly uncertain. In the base case, patients take nilotinib for much less time than dasatinib. Nilotinib is expected to dominate high-dose imatinib, yielding slightly more (0.32) quality-adjusted life years (QALYs) at slightly less cost (£11,100 [pound sterling]) per person. Dasatinib is predicted to provide slightly more (0.53) QALYs at substantially greater cost (£48,900), yielding a very high incremental cost-effectiveness ratio of £91,500 QALY against high-dose imatinib. Cost-effectiveness, however, changes radically under the plausible assumption that the drugs are taken for the same time. For people intolerant to imatinib, nilotinib is expected to yield an incremental cost-effectiveness ratio of £104,700/QALY, and dasatinib £82,600/QALY compared with interferon-α. Further, both drugs represent poor value for money for a range of plausible structural assumptions. CONCLUSIONS: The model should be viewed as an exploratory analysis of the cost-effectiveness of dasatinib and nilotinib because it relies on many assumptions. Whilst clinical data remains immature, the cost-effectiveness of dasatinib and nilotinib for imatinib-resistant people is highly uncertain. Both nilotinib and dasatinib are highly unlikely to be cost-effective versus interferon-α for people intolerant to imatinib.

Updated estimates of survival and cost effectiveness for imatinib versus interferon-alpha plus low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukaemia.

BACKGROUND: For trials in which participants are followed beyond the main study period to assess long-term outcomes, economic evaluations conducted using short-term data should be systematically updated to reflect new information. METHODS: We used 60-month survival data from the IRIS (International Randomized study of Interferon vs STI571) trial to update previously published cost-effectiveness estimates, based on 19 months of follow-up, of imatinib versus interferon (IFN)-alpha plus low-dose cytarabine in patients with chronic-phase chronic myeloid leukaemia. For patients treated with imatinib, we used the 60-month data to calibrate the survival curves generated from the original cost-effectiveness model. We used historical data to model survival for patients randomized to IFNalpha. We updated costs for medical resources using 2006 Medicare reimbursement rates and applied average wholesale prices (AWPs) and wholesale acquisition costs (WACs) to study medications. RESULTS: Five-year survival for patients randomized to imatinib was better than predicted in the original model (89.4% vs 83.2%). We estimated remaining life expectancy with first-line imatinib to be 19.1 life-years (3.8 life-years over the original model) and 15.2 QALYs (3.1 QALYs over the original estimate). Estimates for IFNalpha remained at 9.1 life-years and 6.3 QALYs. When we applied AWPs to study medications, incremental cost-effectiveness ratios (ICERs) were $US 51,800-57,500 per QALY. When we applied WACs, ICERs were $US 42,000-46,200 per QALY. CONCLUSION: Although the analysis revealed that the original survival estimates were conservative, the updated cost-effectiveness ratios were consistent with, or slightly higher than, the original estimates, depending on the method for assigning costs to study medications.

Cost-utility analysis of imatinib mesilate for the treatment of advanced stage chronic myeloid leukaemia.

Imatinib mesilate (Glivec), Novartis Pharmaceuticals) is a novel therapy for the treatment of chronic myeloid leukaemia (CML). We evaluated the cost-effectiveness of imatinib (600 mg daily) when used for the treatment of patients in advanced stages of CML (accelerated phase and blast crisis) against conventional therapies of combination chemotherapy (DAT) and palliative care in hospital or at home. A Markov model simulated the transitions of hypothetical patient cohorts and outcomes were modelled for 5 years from the start of treatment. Costs were estimated from the perspective of the UK National Health Service. Over 5 years, a patient in accelerated phase will, on average, accrue an additional 2.09 QALYs with imatinib compared to conventional therapies, while patients in blast crisis will accrue an additional 0.58 quality-adjusted life-years (QALYs) with imatinib compared to conventional therapies. The costs per additional QALY gained from treatment with imatinib compared with conventional therapies were pound 29344 (accelerated phase) and pound 42239 (blast crisis). The results were particularly sensitive to the price of imatinib, improvements in quality of life, and the duration of haematological responses. We conclude that treatment of CML with imatinib confers considerably greater survival and quality of life than conventional treatments but at a cost.

Cytarabine added to interferon improves the cost-effectiveness of initial therapy for patients with early chronic phase chronic myelogenous leukemia.

The French Chronic Myeloid Leukemia Study Group prospective randomized study results indicate that the addition of cytarabine to alpha interferon (IFN-alpha) increases the rate of major cytogenetic response and prolongs survival in patients with early chronic phase chronic myelogenous leukemia (CML). The French group study design permitted a single crossover to include or discontinue cytarabine or interferon. Endpoints were overall survival, complete hematologic remission (CHR) at six months, and major cytogenetic response at 12 months. We modified a published Markov model that compared IFN-alpha alone to IFN-alpha plus cytarabine and included the possibility of crossover as in the French study. The model permits allogeneic and autologous stem cell transplantation (SCT), and follows cytogenetic response and acceleration of CML through death. Treatment response, toxicity, and survival are drawn from the French Chronic Myeloid Leukemia Study Group population of 810 patients on an intention-to-treat model. Survivals are extended to 62 months based on currently available follow-up. Costs from a United States oncology specialty institution, and state utilities from previous research and a quality-adjusted Time Without Symptoms or Toxicity analysis of the subject study were discounted at 3% per annum. At the median cohort age of 50, cytarabine offers 21 months of added median survival to IFN-alpha, which itself is superior to conventional chemotherapy by 21 months. Cost-effectiveness estimates for cytarabine added to IFN-alpha range from $7,000 per quality-adjusted life year (QALY) to $35,000 per QALY, under all plausible assumptions superior to IFN-alpha alone. The model is sensitive to the quality of life on therapy, as well as to remission rate with additive cytarabine, although the cost-effectiveness calculations are robust over the entire range of clinical assumptions. Based on data from the French study, cytarabine added to IFN-alpha substantially improves the cost-effectiveness of initial therapy for early chronic phase CML.