Multiplex digital PCR enables sensitive detection of resistance to BTK inhibitors.

The advent of BTK inhibitors has been transformative in the management of patients with chronic lymphocytic leukemia or other B-cell lymphoproliferative disorders. However, emergence of BTK or PLCG2 mutations lead to resistance to these compounds and are now a growing concern in clinical practice. Assessing BTK mutations is now becoming a priority to guide the therapeutic decision at further relapse.

Detection of clinically relevant variants in the gene below 10% allelic frequency: A multicenter study by ERIC, the European Research Initiative on CLL.

In chronic lymphocytic leukemia, the reliability of next-generation sequencing (NGS) to detect variants ≤10% allelic frequency (low-VAF) is debated. We tested the ability to detect 23 such variants in 41 different laboratories using their NGS method of choice. The sensitivity was 85.

Inflammatory Waldenström macroglobulinemia is associated with clonal hematopoiesis: a multicentric cohort.

Inflammatory form of Waldenström macroglobulinemia (iWM) predicts outcomes after immuno-chemotherapy and Bruton tyrosine kinase inhibitors, but its origin is unknown. Here, we unravel increased clonal hematopoiesis in patients with iWM (61% vs 23% in noninflammatory WM), suggesting a contribution of environmental cells to iWM.

Cancer associated variant enrichment CAVE, a gene agnostic approach to identify low burden variants in chronic lymphocytic leukemia.

Intratumoral heterogeneity is an important clinical challenge because low burden clones expressing specific genetic alterations drive therapeutic resistance mechanisms. We have developed CAVE (cancer-associated variant enrichment), a gene-agnostic computational tool to identify specific enrichment of low-burden cancer driver variants in next-generation sequencing (NGS) data. For this study, CAVE was applied to TP53 in chronic lymphocytic leukemia (CLL) as a cancer model.

Blinatumomab after R-CHOP bridging therapy for patients with Richter transformation: a phase 2 multicentre trial.

Richter transformation (RT) is an aggressive lymphoma occurring in patients with chronic lymphocytic leukaemia. Here we investigated the anti-CD3/anti-CD19 T-cell-engager blinatumomab after R-CHOP (i.e.