Bortezomib is a chemotherapeutic agent that is frequently used in patients with relapsed or refractory multiple myeloma (MM). Bortezomib works as a reversible proteasome inhibitor, specifically targeting the 26S proteasome within cells.1 The 26S proteasome normally degrades ubiquitinated proteins, which helps maintain homeostasis. Therefore, inhibition of the 26S proteasome prevents proteolysis, leading to disruption of homeostasis via cell cycle arrest and apoptosis.1 There are a multitude of ways to monitor a patient’s responses to bortezomib, however, there is increasing research interest in the responses that may be readily identifiable using flow cytometry and immunophenotyping.
Typically, flow cytometry is utilized in patients with MM in order to determine the different clonal cell populations and their response to therapy.2 Some of the most common markers with abnormal expression analyzed during flow cytometry and immunophenotyping include CD56, CD44, CD28 and CD33.3
CD33 is associated with an overall poor prognosis, while CD56 downregulation and CD44 upregulation is seen in patients with extramedullary spread of MM.4,5 In addition to these associations, MM cells can be classified by their level of maturity with mature plasma cell (MPC)-1 negativity, referring to the most immature type of cells that are refractory to standard chemotherapy.6
A study published by Oka and colleagues aimed to further evaluate how certain immunophenotypes correlate with prognosis in patients with MM who receive bortezomib as an induction therapy.7 This was a retrospective chart review of patients with MM that was conducted at a single center in Japan between 2007 and 2017. All patients were treated with bortezomib and dexamethasone. Data from a total of 118 patients were reviewed in the study.
Immunophenotyping revealed the following results with respect to protein markers: 68.6% with CD56, 18.6% with CD33, 23.7% with CD45, 5% with CD20 and 82.2% with MPC-1. Patients with CD33+ were more likely to have calcium levels higher than 11 (P =.023) and LDH higher than 211 (P <.001) when compared with their CD33-negative counterparts.