Experts outline PET-CT, biopsy and mutation testing to guide therapy in relapsed CLL

In a recent discussion, clinicians described the workup for patients with progressive chronic lymphocytic leukemia (CLL). They emphasized using PET‑CT imaging and excisional lymph node biopsy when Richter transformation is suspected, noting that markedly high SUVmax values would prompt biopsy.

The speakers highlighted clinical signs that raise concern for transformation, such as rapid symptom worsening, new lymphadenopathy, and discordant lactate dehydrogenase elevations. In the presented case, these features were absent, so transformation was not pursued.

When disease progresses on covalent BTK inhibitors, the panel recommended resistance mutational testing. The most common finding is a C481S mutation at the drug‑binding site, supporting a switch to non‑covalent BTK inhibitors. Additional testing may reveal rare mutations, and in this patient an acquired TP53 mutation helped shape second‑line treatment decisions.

Overall, the experts stressed that integrating imaging, pathology, and molecular profiling is essential for selecting the next therapeutic approach in relapsed CLL patients.