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Tyrosine kinase inhibitors (TKIs) have improved CML prognosis, yet survival remains poor in patients on ≥3rd line therapy2,3
Many patients on TKIs face treatment failure or discontinuation due to intolerance, with up to half of patients discontinuing 1st line imatinib within 5 years.3
During 2nd line treatment:3
of patients fail to achieve major molecular response (MMR)3
of patients fail to achieve complete cytogenetic response (CCyR) within 2 years3
In CML patients, a low 8-year overall survival was associated with being on ≥3rd-line of treatment.*2
Approximately 2/3 of those who had at least 1 TKI switch was due to resistance*4 (n=73/113)
8-year overall survival, N=902
Adapted from Bosi GR, et al. 2019.2
Optimal monitoring is important to assess treatment benefits and inform the decision to switch.5,6 When a TKI fails, timely switching can limit the progression of disease6
A 2nd generation TKI may have limited benefit in a ≥3L setting, after the failure of another 2nd generation TKI and 1st generation TKI prior.3 Patients in ≥3L of treatment may need a different mechanism of action to optimise outcomes.2,7–9
“You can end up running out of options for patients who experience side effects. Then you need to consider transplant after 4th line or chemotherapy options”
– Adapted from haematologist quote11
“In a year I had gone from taking one drug and living a normal life to having zero options”
– Adapted from 5L CML patient quote12
SCEMBLIX is the first and only STAMP inhibitor, specifically targeting the ABL1 myristoyl pocket10,13,14
SCEMBLIX demonstrated superior efficacy and a favourable safety profile vs bosutinib at Week 24†13
The ASCEMBL trial did not restrict to Ph+ patients with CP-CML. SCEMBLIX is indicated in adult with Ph+ CP-CML previously treated with two or more tyrosine kinase inhibitors and without a known T315I mutation.1,13
*Data from a retrospective, non-interventional study conducted at 21 UK NHS secondary and tertiary care centres on 257 patients with CML.2
†A total of 233 patients with CML in chronic phase, all of whom previously received at least 2 TKIs. Participants were randomised to asciminib (n=157) or bosutinib (n=76). Median follow-up was 14.9 months. The MMR rate at Week 24 was 25.5% with asciminib and 13.2% with bosutinib. The difference in MMR rate between treatment arms, after adjusting for MCyR at baseline, was 12.2% (95% CI: 2.19-22.30; 2-sided P=0.029). Fewer grade ≥3 adverse events (50.6% vs 60.5%) and adverse events leading to treatment discontinuation (5.8% vs 21.1%) occurred with asciminib than with bosutinib.13
ATP, adenosine triphosphate; CCyR, complete cytogenetic response; CI, confidence interval; CML, chronic myeloid leukaemia; MCyR, major cytogenetic response; MMR, major molecular response; MOA, mechanism of action; NHS, National Health Service; Ph+, Philadelphia chromosome positive; STAMP, specifically targeting the ABL1 myristoyl pocket; TKI, tyrosine kinase inhibitor
For further information please refer to the Summary of Product Characteristics.
References
- SCEMBLIX (asciminib) SmPC, 2023.
- Bosi GR, et al. Hematol Transfus Cell Ther 2019;41(3):222–228.
- Cortes JE and Lang F. J Hematol Oncol 2021;14(1):44.
- Milojkovic D, et al. Br J Haematol 2021;192:62–74.
- Smith G, et al. Br J Haematol 2020;191:171–193.
- Hochhaus A, et al. Leukaemia 2020;34:1495–1502.
- Soverini S, et al. Blood 2009;114(10):2168–2171.
- Garg RJ, et al. Blood 2009;114(20):4361–4368.
- Ibrahim AR, et al. Blood 2010;116(25):5497–5500.
- Schoepfer J, et al. J Med Chem 2018;61(18):8120–8135.
- Novartis data on file; Asc001.
- Novartis data on file; Hae003.
- Réa D, et al. Blood 2021;138(21):2031–2041.
- Redaelli S, et al. J Clin Oncol 2009;27(3):469–471.