Short telomeres linked to shorter progression-free survival with first-line venetoclax in CLL

An analysis published in Blood examined whether telomere length retains prognostic relevance in chronic lymphocytic leukemia (CLL) treated with targeted therapies. Researchers measured telomere length by quantitative PCR in 917 samples from treatment-naïve patients without TP53 aberrations in GAIA/CLL13, which compared venetoclax plus rituximab (RV), obinutuzumab (GV), or obinutuzumab and ibrutinib (GIV) against chemoimmunotherapy. They also analyzed samples from 41 treatment-naïve patients with TP53 aberrations receiving GIV in CLL2-GIVe.

Median telomere lengths were 4.0 kb in GAIA/CLL13 and 2.8 kb in CLL2-GIVe. Using a GAIA/CLL13-derived cutoff of 4.17 kb, short telomeres were associated with adverse clinical and genetic features, including unmutated IGHV, del(11q), and karyotypic complexity. Short telomeres were associated with shorter progression-free survival in all four GAIA/CLL13 treatment arms (all P<0.01) and in CLL2-GIVe using its median as the cutoff (P=0.04). An overall survival association was observed only in the chemoimmunotherapy arm (P=0.024).

Multivariable analysis suggested telomere length was an independent prognostic factor for progression-free survival in GAIA/CLL13. These findings support its potential role in risk stratification, but do not establish that telomere-guided treatment selection improves outcomes. The available abstract provides no hazard ratios or absolute survival estimates, and the TP53-aberrant cohort was small.