Therapy for patients with chronic phase-chronic myeloid leukemia previously treated with ⩾2 tyrosine kinase inhibitors: a systematic literature review.

Background: ATP-competitive tyrosine kinase inhibitors (TKIs) are the current standard of care for patients with chronic phase-chronic myeloid leukemia (CP-CML) in the first-line and second-line (2 L) setting. Treatment after 2 L is not clearly established. Objective: The objective of this study was to summarize the available evidence to compare the efficacy and safety of interventions in the treatment of CP-CML patients who had received ⩾2 prior TKIs. Design: A systematic literature review was performed. Data source and methods: A systematic literature review (SLR) of studies published until May 2021, reporting clinical outcomes in adult patients with CP-CML who had received ⩾ 2 prior TKIs was performed. Studies were identified through the database searches via Ovid platform (Embase, MEDLINE Epub Ahead of Print, In-Process and Other Non-Indexed Citations, and Cochrane Central Register of Controlled Trials), the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), bibliographic search of relevant reviews, and proceedings from the previous 3 years of the key conferences in the field of oncology. Results: Our search identified 38 relevant studies. Among the identified studies of the current third-line treatments, the major molecular response (MMR) rate for ponatinib was 19.0-66.7%, 23.3-25.5% for asciminib, 19.2% for omacetaxine, and 13.2% for bosutinib at 6 months. The complete cytogenetic response (CCyR) rate was 21.4-64.8% for ponatinib, 38.7-40.8% for asciminib, 18-24.2% for bosutinib, and 16.1% for omacetaxine at 6 months. Conclusion: The findings from current SLR demonstrated the lack of data for patients with CML treated with ⩾2 TKIs. TKIs such as asciminib, ponatinib, and bosutinib are valid options for those patients. Further research is needed to identify the best treatment option for patients with CML receiving later lines of therapy.

Matching-adjusted indirect comparison of asciminib versus other treatments in chronic-phase chronic myeloid leukemia after failure of two prior tyrosine kinase inhibitors.

PURPOSE: The current standard of care for chronic-phase chronic myeloid leukemia (CP-CML) is tyrosine kinase inhibitors (TKIs). Treatment recommendations are unclear for CP-CML failing ≥ 2 lines of treatment, partly due to the paucity of head-to-head trials evaluating TKIs. Thus, matching-adjusted indirect comparisons (MAICs) were conducted to compare asciminib with competing TKIs in third- or later line (≥ 3L) CP-CML. METHODS: Individual patient-level data for asciminib (ASCEMBL; follow-up: ≥ 48 weeks) and published aggregate data for comparator TKIs (ponatinib, nilotinib, and dasatinib) informed the analyses. Major molecular response (MMR), complete cytogenetic response (CCyR), and time to treatment discontinuation (TTD) were assessed, where feasible. RESULTS: Asciminib was associated with statistically significant improvements in MMR by 6 (relative risk [RR]: 1.55; 95% confidence interval [CI]: 1.02, 2.36) and 12 months (RR: 1.48; 95% CI: 1.03, 2.14) vs ponatinib. For CCyR, the results vs ponatinib were similar by 6 (RR: 1.11; 95% CI: 0.81, 1.52) and 12 months (RR: 0.97; 95% CI: 0.73, 1.28). Asciminib was associated with improvements in MMR by 6 months vs dasatinib but with a CI overlapping one (RR 1.52; 95% CI: 0.66, 3.53). Asciminib was associated with statistically significant improvements in CCyR by 6 (RR: 3.57; 95% CI: 1.42, 8.98) and 12 months (RR: 2.03; 95% CI: 1.12, 3.67) vs nilotinib/dasatinib. Median TTD was unreached for asciminib in ASCEMBL. However, post-adjustment asciminib implied prolonged TTD vs nilotinib and dasatinib, but not vs ponatinib. CONCLUSION: These analyses demonstrate favorable outcomes with asciminib versus competing TKIs, highlighting its therapeutic potential in ≥ 3L CP-CML.

A Systematic Literature Review of the Economic Evaluations of Treatments for Patients with Chronic Myeloid Leukemia.

BACKGROUND AND OBJECTIVES: The management of chronic myeloid leukemia is associated with an extensive economic burden, and as novel interventions are being tested in this disease, understanding the comparative effectiveness is of interest. Findings and conclusions of this important issue continue to evolve with improvements in clinical research and economic understanding. This systematic literature review aims to conduct a comprehensive assessment of economic evaluations in chronic phase chronic myeloid leukemia. METHODS: Embase®, MEDLINE®, and the National Health Service Economic Evaluation Database were searched on 4 July, 2022 to identify economic evaluations of chronic myeloid leukemia. Health technology assessment websites and key conference proceedings were also searched. Economic evaluations comparing treatment options in adult patients with chronic phase chronic myeloid leukemia were included. The quality of the studies were assessed using Drummond's checklists. RESULTS: The search retrieved 47 studies and 16 health technology assessments that fulfilled the eligibility criteria. Most were cost-utility analyses (23 studies and 11 health technology assessments) and were from the USA (n = 15) and China (n = 7). Twenty-seven studies and six health technology assessments included only patients with chronic phase chronic myeloid leukemia. Most models had a Markov structure, a 1 year to lifetime time horizon, and a 1-month cycle length. Commonly assessed treatments were various tyrosine kinase inhibitors (imatinib, nilotinib, dasatinib, bosutinib, and ponatinib) and other interventions such as interferon-α, hydroxyurea, and allogeneic stem cell transplant. CONCLUSIONS: In patients with newly diagnosed chronic myeloid leukemia, imatinib regimens were cost effective, mostly owing to the availability of generics. Nilotinib and dasatinib were generally cost effective as second-line agents for patients who were resistant or intolerant to imatinib. Though progress has been made to better characterize the cost effectiveness of first-line and second-line chronic myeloid leukemia therapies, the paucity of published cost-effectiveness studies of third-line treatments increases the uncertainty associated with economic evaluations of later lines of therapy.