Expression levels and patterns of B‐cell maturation antigen in newly diagnosed and relapsed multiple myeloma patients from Indian subcontinent

Abstract

Background Many novel therapies are being evaluated for the treatment of Multiple myeloma (MM). The cell‐surface protein B‐cell maturation antigen (BCMA, CD269) has recently emerged as a promising target for CAR‐T cell and monoclonal‐antibody therapies in MM. However, the knowledge of the BCMA expression‐pattern in myeloma patients from the Indian subcontinent is still not available. We present an in‐depth study of BCMA expression‐pattern on abnormal plasma cells (aPC) in Indian MM patients. Methods We studied BM samples from 217 MM patients (211‐new and 6‐relapsed) with a median age of 56 years (range, 30–78 years & M:F‐2.29) and 20 control samples. Expression levels/patterns of CD269 (clone‐19f2) were evaluated in aPCs from MM patients and in normal PCs (nPC) from uninvolved staging bone marrow samples (controls) using multicolor flow cytometry (MFC). Expression‐level of CD269 was determined as a ratio of mean fluorescent intensity (MFI‐R) of CD269 in PCs to that of non‐B‐lymphocytes and expression‐pattern (homogenous/heterogeneous) as coefficient‐of‐variation of immunofluorescence (CVIF). Results Median (range) percentage of CD269‐positive abnormal‐PCs in total PCs was 71.6% (0.49–99.29%). The MFI‐R (median, range) of CD269 was significantly higher in aPCs (4.13, 1.12–26.88) than nPCs (3.33, 1.23–12.87), p < .0001. Median (range) MFI of CD269 at diagnosis and relapse were 2.39 (0.77–9.57) and 2.66 (2.15–3.23) respectively. CD269 levels were similar at diagnosis and relapse, p = .5529. Conclusions We demonstrated that BCMA/CD269 is highly expressed in aPCs from a majority of MM patients, both at diagnosis and relapse. Thus, BCMA is a valuable target for therapy for Indian MM patients.

Issue highlights—July 2023

“…Achieving MRD negativity in MM is crucial for improved patient outcomes. In newly diagnosed and relapsed MM, a high percentage of BCMA‐positive abnormal plasma cells was found, supporting its potential as a target for CAR‐T cell and monoclonal‐antibody therapies (Sriram et al, 2022). Aberrancies in polyclonal plasma cells and immunomodulation in neoplastic plasma cells post‐therapy were identified in another study, underscoring the importance of validating MRD assays under normal and reactive conditions (Das et al, 2022).…”

Issue highlights—May 2024

“…However, the knowledge of the BCMA expression pattern in myeloma patients from the Indian subcontinent was not available at that time. A study presented by Sriram et al (2022) is an in‐depth report of BCMA expression on abnormal plasma cells (APC) in Indian MM patients. In the UK, in a 2022 MRD assessment, MM was not incorporated into routine clinical use outside of trials.…”