ADOLESCENT and young adult (AYA) patients with chronic myeloid leukaemia (CML) experience significantly higher rates of first-line tyrosine kinase inhibitor (TKI) treatment failure due to resistance than older patients, despite similar overall rates of therapy switching, according to data from a large Catalan registry analysis.
CML Resistance Emerges Early
A study presented at EHA 2026 examined 318 patients with Philadelphia chromosome-positive (Ph+) CML treated with TKI therapy, including 111 AYA patients and 207 patients aged 40 years or older. Researchers sought to understand whether differences in treatment outcomes between younger and older patients could be explained by patterns of TKI switching, particularly resistance and intolerance.
Among AYA patients, 61% were classified as low-risk according to the Sokal score, compared with 47% of older patients. Most patients in both groups received imatinib as first-line treatment, while a smaller proportion received second-generation TKIs (2G-TKIs). Median follow-up was substantially longer in the AYA cohort at 118 months, compared with 60.5 months in older patients, providing an extended view of long-term treatment outcomes.
TKI Resistance Drives CML Switching
Overall rates of first-line TKI switching were comparable between age groups, occurring in 42% of AYA patients and 46% of older patients. However, the reasons for switching differed significantly.
Resistance accounted for 32% of first-line switches in AYA patients, compared with 19% among older patients. The median time to switching due to resistance was 17 months in younger patients and 14.5 months in older individuals. In contrast, intolerance-related switching was significantly less common in the AYA cohort, affecting 9.9% of patients versus 24% of those aged 40 years or older.
These findings suggest that treatment failure in younger patients is more likely to be driven by inadequate disease control than by adverse events, highlighting potentially distinct biological or clinical characteristics within this population.
CML Treatment Challenges Persist
Switching remained frequent among AYA patients in subsequent lines of therapy, occurring in 48% of second-line, 28.5% of third-line and 75% of fourth-line treatment courses. While resistance was the predominant reason for first-line switching, intolerance became the leading driver in later treatment lines.
Notably, upfront use of 2G-TKIs did not appear to reduce resistance-related first-line switching among AYA patients, although the number of patients in this subgroup was limited. The findings raise questions about whether current treatment strategies adequately address the needs of younger individuals with CML.
In summary, AYA CML may represent a clinically distinct subgroup. Prospective studies are now needed to evaluate early optimisation strategies and alternative treatment approaches aimed at reducing resistance and improving long-term outcomes.
Reference
Marti JH et al. Higher first line TKI resistance in adolescents and young adults (AYA) with chronic myeloid leukemia. evidence from a population-based registry. Abstract EHA-4011. EHA 2026 Congress. 11-14 June 2026.
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