During the past few years several new treatment approaches have been developed for B-cell & plasma cell malignancies, including therapeutic antibodies (e.g. CD19/CD38/CD319) and signal pathway inhibitors (e.g. Ibrutinib/Idelalisib). Therapeutic activity depends on target expression, e.g. the efficacy of Ibrutinib in Waldenstroms Macroglobulinemia correlates with the presence of the driver MYD88 L265P mutation, and it is therefore essential that the diagnostic laboratory work-up takes potential treatment approaches into account. For CLL, the lack of a pathognomonic molecular abnormality means that diagnosis continues to rely heavily on the cellular immunophenotype and the ERIC & ESCCA groups have recently complete a project to identify reproducible criteria and consensus on markers recommended for the diagnosis of CLL by flow cytometry.

New treatments can also have a significant impact on the approach to monitoring disease during and after treatment, due to loss of epitope expression/availability with antibody therapy &/or phenotypic shift with pathway inhibitors. In CLL it remains possible to separate neoplastic cells from normal B-cells but loss of detectable CD19 expression can impair B-cell detection. HLA-DR is strongly expressed by almost all normal and neoplastic B-cells and also persists during BCR-pathway inhibitor treatment and can be combined with CD22/ROR1 expression to detect residual CLL in patients with weak/undetectable CD19 expression. In myeloma the use of the anti-CD38 therapeutic antibody daratumumab impairs detection of residual disease and alternative approaches to plasma cell gating are required, e.g. using multi-epitope CD38 antibody reagents, additional surface markers such as CD229/CD319, or intracellular markers such as VS38c or IRF4. 

The presentation will use specific cases to highlight laboratory issues in the diagnosis of mature B-cell and plasma cell malignancies as well as the issue of phenotypic changes during treatment and potential approaches to maintain the capability to monitor disease.