CML in the Very Elderly: The Impact of Comorbidities and TKI Selection in a Real-life Multicenter Study

Author:

Rozental Alon1,Halperin Erez1,Leibovitch Chiya2,Barzili Meirav3,Koren-Michowitz Maya4,Duek Adrian5,Rozovski Uri1,Extermann Martine6,Raanani Pia1,Shacham-Abulafia Adi1

Affiliation:

1. Rabin Medical Center

2. Ashdod Hospital

3. Tel Aviv Medical Center

4. Tel Aviv University

5. Assuta Medical Center

6. H. Lee Moffitt Cancer Center

Abstract

Abstract

Tyrosine kinase inhibitors (TKIs) have greatly improved chronic myeloid leukemia (CML) treatments, with survival rates close to the general population. Yet, for the very elderly, robust data remains limited. This study focused on assessing comorbidities, treatment approaches, responses, and survival for elderly CML patients. Our study was conducted on 123 elderly (≥ 75 years) CML patients across four centers in Israel and Moffitt Cancer Center, USA. The median age at diagnosis was 79.1 years, with 44.7% being octogenarians. Comorbidities were very common; cardiovascular risk factors (60%), cardiovascular diseases (42%), with a median age-adjusted Charlson Comorbidity Index (aaCCI) of 5. Imatinib was the leading first-line therapy (69%), while the use of second-generation TKIs increased post-2010. Most patients achieved a major molecular response (MMR, 75%), and more than half achieved a deep molecular response (DMR, 57%). Over half (53.6%) of patients moved to second-line, and nearly a quarter (23.5%) to third-line treatments, primarily due to intolerance. Overall survival (OS) was notably longer in patients with an aaCCI score below 5, for those receiving second-generation TKIs as initial therapy, and in patients who attained DMR. Contrary to expectations, the Israeli cohort showed a shorter actual life expectancy than projected, suggesting a larger impact of CML on elderly survival. In summary, imatinib remains the main initial treatment, but second-generation TKIs are on the rise among elderly CML patients. Outcomes in elderly CML patients depend on comorbidities, TKI type, response, and age, underscoring the need for personalized therapy and additional research on TKI effectiveness and safety.

Publisher

Research Square Platform LLC

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