Minimal residual disease (MRD) in Waldenström macroglobulinaemia (WM): Impact on survival outcomes with rituximab-based therapies.

Minimal residual disease (MRD) is an independent predictor of survival outcomes in many haematological malignancies, most notably myeloma and CLL. Rituximab-based regimens are widely used as primary therapy in WM with excellent response durations noted in many patients despite the apparent rarity of complete responses (CR). We have previously demonstrated that rituximab-based therapies can result in depletion of monotypic B-cells but a persistence of CD20- plasma cells. This phenomenon can result in delayed serological responses and may also explain the low incidence of CR. We have therefore developed a flow cytometry assay (based upon the unique immunophenotypic profile of WM B-cells) in order to quantify the extent of B-cell depletion with rituximab-based therapies. This assay has a limit of detection of 0.004%. Aim: To determine the prognostic significance of residual neoplastic B-cells in WM following rituximab-based therapy in the context of the UK R2W clinical trial. Method: 60 treatment-naïve WM patients were enrolled onto the study, which involved 2:1 randomisation to treatment with BCR (Bortezomib; Cyclophosphamide; Rituximab) or FCR (Fludarabine; Cyclophosphamide; Rituximab). Bone marrow aspirate and peripheral blood samples were obtained at baseline, post 3 cycles of treatment and at 3 months following the end of therapy (EOT).