Page 22 - Haematologica Vol. 109 - July 2024

EDITORIAL O. Al-Sawaf
Figure 1. Landscape and impact of mutations with zanubrutinib treatment. cBTKi: covalent Bruton tyrosine kinase inhibitor.
the use of ibrutinib or acalabrutinib.7 This observation is of high clinical relevance, as non-covalent BTK inhibitors, which have demonstrated efficacy also in the presence of C481S mutations, could be adversely affected in the con- text of L528W mutations.8 Thus, the mutational pattern can have clinical implications regarding the sequence of giving zanubrutinib before or after pirtobrutinib. In the study by Xu et al. no L528W mutations were found in patients receiving zanubrutinib after prior ibrutinib or acalabruti- nib therapy. With the caveat that the number of relapse samples sequenced was limited, this study at least does not suggest a particular over-enrichment of this variant in a cohort treated with ibrutinib/acalabrutinib followed by zanubrutinib.
Several open questions remain. As the number of patients progressing on zanubrutinib was limited in this cohort and the follow-up was relatively short, statistical analyses of prognostic factors were still heavily underpowered. Fur-
References
1. Xu L SM, Flinn IW, et al. Genomic landscape of patients in a phase II study of zanubrutinib in ibrutinib- and/or acalabrutinib-intolerant patients with B-cell malignancies. Haematologica. 2024;109(7):2284-2289.
thermore, our understanding of the clonal evolutionary patterns for patients discontinuing a BTK inhibitor due to toxicity and then undergoing treatment with a different BTK inhibitor is still incomplete. Most insights generated in this study are derived from the patients with chronic lympho- cytic leukemia, from whom material for sequencing could be obtained from peripheral blood. However, the mutational patterns in nodal entities, such as mantle cell lymphoma and marginal zone lymphoma, are still understudied. Fi- nally, given limited sample size and the heterogeneity of reasons for discontinuing treatment, further studies are required to better understand clinical and genomic features that might be associated with toxicity and intolerance to targeted agents.
Disclosures
No conflicts of interest to disclose.
2. Muñoz J, Sarosiek S, Castillo JJ. Managing ibrutinib-intolerant patients with B-cell malignancies. Oncologist. 2023;28(4):309-318.
3. Stephens DM. NCCN guidelines update: chronic lymphocytic
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