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. 2022 Jul 28;140(4):401-405.
doi: 10.1182/blood.2021015132.

Subclonal evolution of CLL driver mutations is associated with relapse in ibrutinib- and acalabrutinib-treated patients

Gage S Black  1   2 , Xiaomeng Huang  1   2 , Yi Qiao  1   2 , Szabolcs Tarapcsak  1   2 , Kerry A Rogers  3 , Shrilekha Misra  3 , John C Byrd  4 , Gabor T Marth  1   2 , Deborah M Stephens  5 , Jennifer A Woyach  3
Affiliations

Subclonal evolution of CLL driver mutations is associated with relapse in ibrutinib- and acalabrutinib-treated patients

Gage S Black et al. Blood. .
No abstract available

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Figures

Figure 1.
Figure 1.
An overview of the clonal evolution identified in this study. (A) The patterns of clonal evolution identified, with an example of 1 patient from each pattern. This includes patient 28 (no evolution), patient 26 (new clone emergence), patient 27 (clonal selection), and patient 32 (clonal replacement). Gene names represent mutated CLL-relevant genes found within the indicated subclone. A, B, C, and D represent a unique cluster of variants seen within a given subclone that distinguishes it from other subclones. Richter’s transformation patients account for 4/19 of those with no evolution, 3/11 with new clone emergence, and 1/5 with clonal selection. (B) A breakdown of the clonal evolution found within each treatment cohort. Each cohort is separated into patients who continued to respond to the given BTKi and those who relapsed during BTKi treatment. (C) A Fisher’s exact test comparing the presence or absence of evolving subclones containing CLL-driver mutations to the treatment outcome of all patients.
Figure 2.
Figure 2.
Kaplan-Meier curve showing the probability of relapse-free survival over time. A landmark was set at year 2 to group patients with or without the evolution of subclones containing CLL-relevant mutations up to that point. The red line includes any patient with baseline TP53 mutations, the green line includes patients without baseline TP53 mutations who had at least one evolving CLL-relevant mutation in the first 2 years of treatment, and the blue line includes patients without baseline TP53 mutations or evolving CLL-relevant mutations at year 2. The x-axis represents the relapse-free survival time since the second year of treatment. There is a significant difference in the relapse-free survival of patients who do not have CLL-relevant evolution in the first 2 years compared with those who do (log-rank P = .0004 when comparing the green and blue lines).
See this image and copyright information in PMC

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