Article

TKI Therapy for Chronic-Phase CML Leads to Comparable Outcomes for AYAs and Older Adults

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A retrospective study found that adolescents and young adults (AYA) receiving tyrosine kinase inhibitors (TKI) therapy for chronic-phase chronic myeloid leukemia (CML) had similar prognoses to older patients despite also showing higher tumor burden at diagnosis.

Tyrosine kinase inhibitors (TKIs) have significantly improved outcomes for patients with chronic-phase chronic myeloid leukemia (CML-CP), most of whom are older or elderly adults. But when it comes to the smaller population of adolescent and young adults (AYAs) with CML-CP, few studies have analyzed outcomes for patients receiving TKIs. A retrospective study published in Annals of Medicine found that AYAs receiving TKI therapy had similar prognoses to older patients despite also showing higher tumor burden at diagnosis.

AYAs, defined as those aged 15 to 39 years, account for approximately half of the world population. They represent a relatively small but still significant number of cancer patients, and outcomes in this group overall tend to be worse than outcomes for younger or older patients.

“Many AYA patients continue to experience inferior outcomes in comparison to younger and older age groups for many reasons,” the authors wrote. “One of the reasons is reported to be low clinical trial participation resulting in a low rate of tumor specimen acquisition for research; thus, there is less understanding of the biological features in this patient population. ”A lack of standardized therapy approaches, poor compliance, fewer medical check-up visits, insurance issues, and other issues are also potential barriers to efficient diagnosis and care for AYAs with cancer, including CML-CP.

The study compared the clinical features, treatment responses, and long-term outcomes of 360 patients 18 years of age or older with CML-CP using data from the CML Cooperative Study Group. Of the overall cohort, 42 patients (11.7%) were classified as AYA (aged 18 to 29) at the time of diagnosis. Compared with the older patients, the AYA cohort were more likely to be classified as high-risk and showed larger spleen sizes, higher white blood cell counts, higher lymphocyte percentages, higher blast percentages in peripheral blood, and lower hemoglobin levels. The median observation period was 76 months in the AYA cohort and 66 months in the older group.

In the AYA group, 24 patients (57.1%) received imatinib as initial treatment, 13 (31%) received dasatinib, and 5 (11.9%) received nilotinib. Among older patients, 158 (49.7%), 85 (26.7%) and 75 (23.6%) were initially treated with imatinib, dasatinib and nilotinib, respectively. Treatment responses were similar between the AYA and older patients, with comparable incidence of major molecular response (MMR) and deep molecular response (DMR) in both groups.

Event-free survival (EFS) and overall survival (OS) rates were very similar between the cohorts, as were the rates of transformation into accelerated phase or blast phase CML. Overall, the long-term outcomes were not significantly different between the cohorts.

A sub-analysis based on the initial therapy patients received did not show any significant differences between EFS and OS rates for patients treated with imatinib, a first-generation TKI, versus second-generation TKIs.

Taken together, the findings suggest that AYAs and older patients with CML-CP who are treated with TKIs face similar prognoses, although younger patients tend to have a higher tumor burden at diagnosis. Further studies to identify the biological and non-biological factors affecting AYA patients with CML-CP on TKIs can help improve management and outcomes, the authors concluded.

Reference

Nishiyama-Fujita Y, Nakazato T, Iriyama N, et al. Outcomes of adolescents and young adults with chronic-phase chronic myeloid leukaemia treated with tyrosine kinase inhibitors. Ann Med. Published online April 29, 2022. doi:10.1080/07853890.2022.2069280

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