Flow cytometry has been indispensable in diagnosing B cell lymphoma and plasma cell neoplasms. The advances in novel multicolor flow cytometry have also made this technology a robust tool for monitoring minimal/measurable residual disease in chronic lymphocytic leukemia and multiple myeloma. However, challenges using conventional gating strategies to isolate neoplastic B or plasma cells are emerging due to the rapidly increasing number of antibody therapeutics targeting single or multiple classic B/plasma cell‐lineage markers, such as CD19, CD20, and CD22 in B cells and CD38 in plasma cells. This review is the first of a two‐part series that summarizes the most current targeted therapies used in B and plasma cell neoplasms and proposes detailed alternative approaches to overcome post‐targeted therapy analysis challenges by flow cytometry. The second review in this series (Chen et al.) focuses on challenges encountered in the use of targeted therapy in precursor B cell neoplasms.
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