VS38 as a promising CD38 substitute antibody for flow cytometric detection of plasma cells in the daratumumab era

Mizuta, Shumpei; Kawata, Takahito; Kawabata, Hiroshi; Yamane, Noriko; Mononobe, Saya; Komai, Takao; Koba, Yusuke; Ukyo, Naoya; Tamekane, Akira; Watanabe, Mitsumasa

doi:10.1007/s12185-019-02685-z

Cited by 21 publications

(19 citation statements)

References 21 publications

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“…(an intracytoplasmic antigen of 63 kilodaltons presents on the rough endoplasmic reticulum) has also been proposed. 52 The utility of VS38c assumes that neoplastic PCs will express CLIMP-63 at a much higher level than normal PC and other leucocyte subsets because of their heightened secretory mechanisms. We and others have shown that while VS38 is highly expressed in most PCs, it is also expressed by other haematopoietic cells including monocytes, myeloid cells, and a subpopulation of B cells.…”

Section: Current Challeng E Smentioning

confidence: 99%

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Evaluation of measurable residual disease in multiple myeloma by multiparametric flow cytometry: Current paradigm, guidelines, and future applications

Soh

Wallace

2021

Int J Lab Hematology

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Multiple myeloma (MM) is a heterogeneous group of mature B‐cell diseases that are typically characterized by the presence and accumulation of abnormal plasma cells (PCs), which results in the excess production of monoclonal immunoglobulin and/or light chain found in the serum and/or urine. Multiparametric flow cytometry (MFC) is an indispensable tool to supplement the diagnosis, classification and monitoring of the disease due to its high patient applicability, excellent sensitivity and encouraging results from various clinical trials. In this regard, minimal or, more appropriately, measurable residual disease (MRD) negativity by MFC has been recognized as a powerful predictor of favourable long‐term outcomes. Before flow cytometry can be effectively implemented in the clinical setting for MM MRD testing, sample preparation, panel configuration, analysis and gating strategies must be optimized to ensure accurate results. This manuscript will discuss the current consensus guidelines for flow cytometric processing of samples and reporting of results for MM MRD testing. We also discuss alternative approaches to detect plasma cells in the presence of daratumumab treatment. Finally, there is a lack of information describing the subclonal distribution of myeloma cells based on their protein expression. The advent of high‐dimensional analysis may assist in following the evolution of antigen expression patterns on abnormal plasma cells in patients with relapsed/refractory disease. This in turn can help identify clonal subtypes that are more aggressive for potential informed decision. An analysis using t‐SNE to identify the emergence of PCs subclones by MFC, along with the analysis of their immunophenotypic profiles are presented as a future perspective.

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Section: Current Challeng E Smentioning

confidence: 99%

“…We and others have shown that while VS38 is highly expressed in most PCs, it is also expressed by other haematopoietic cells including monocytes, myeloid cells, and a subpopulation of B cells. 50,52…”

Section: Current Challeng E Smentioning

confidence: 99%

Evaluation of measurable residual disease in multiple myeloma by multiparametric flow cytometry: Current paradigm, guidelines, and future applications

Soh

Wallace

2021

Int J Lab Hematology

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“…The most promising marker to date has been VS38c, 38,46 which targets cytoskeleton-linking membrane protein (CLIMP-63)/ cytoskeleton-associated protein 4 (CKAP4) (also known as p63, not to be confused with the tumor suppressor gene). This protein is localized to the rough endoplasmic reticulum (RER), and flow cytometric detection requires membrane permeabilization (already and conveniently required for the detection of light chain restriction in plasma cells).…”

Section: Solutionsmentioning

confidence: 99%

Flow cytometric myeloma measurable residual disease testing in the era of targeted therapies

2021

Int J Lab Hematology

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Therapies in myeloma are rapidly advancing with a host of new targeted therapies coming to market. While these drugs offer significant survival benefits and better side‐effect profiles compared with conventional chemotherapeutics, they raise significant difficulties in monitoring post‐therapy disease status by flow cytometry due to assay interference and/or selection of phenotypically different sub‐clones. The principal culprit, anti‐CD38 monoclonal antibodies, limits the ability to detect plasma cells based on classical CD38/CD45 gating. Other markers, such as CD138, are known to be suboptimal by flow cytometry. Various techniques have been proposed to overcome this problem. The most promising of these techniques has been the marker VS38c, a monoclonal antibody targeting an endoplasmic reticulum protein which has shown high sensitivity for plasma cells. Alternative techniques for gating plasma cells, while variably effective in the near term are already the subject of several targeted therapies rendering their usefulness limited in the longer term. Likewise, future targets of these therapies may render present aberrancy markers ineffective in MRD testing. These therapies pose challenges that must be overcome with new markers and novel panels in order for flow cytometric MRD testing to remain relevant.

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“…Alternatives include evaluating for MRD by NGS or alternative anti-CD38 antibodies, such as vs38. 59 60 Additionally, the Hydrashift 2/4 dara is an FDA-approved assay to mitigate antibody interference. 61 Antibody interference testing is unnecessary for non-IgG kappa isotype patients, patients with detectable disease by free light chain (FLC) or Bence Jones protein (BJP), or patients with an M-spike >0.2 g/dL by serum protein electrophoresis (SPEP).…”

Section: Daratumumabmentioning

confidence: 99%

The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of multiple myeloma

Shah

Aiello

Avigan

et al. 2020

J Immunother Cancer

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Outcomes in multiple myeloma (MM) have improved dramatically in the last two decades with the advent of novel therapies including immunomodulatory agents (IMiDs), proteasome inhibitors and monoclonal antibodies. In recent years, immunotherapy for the treatment of MM has advanced rapidly, with the approval of new targeted agents and monoclonal antibodies directed against myeloma cell-surface antigens, as well as maturing data from late stage trials of chimeric antigen receptor CAR T cells. Therapies that engage the immune system to treat myeloma offer significant clinical benefits with durable responses and manageable toxicity profiles, however, the appropriate use of these immunotherapy agents can present unique challenges for practicing physicians. Therefore, the Society for Immunotherapy of Cancer convened an expert panel, which met to consider the current role of approved and emerging immunotherapy agents in MM and provide guidance to the oncology community by developing consensus recommendations. As immunotherapy evolves as a therapeutic option for the treatment of MM, these guidelines will be updated.

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VS38 as a promising CD38 substitute antibody for flow cytometric detection of plasma cells in the daratumumab era

Cited by 21 publications

References 21 publications

Evaluation of measurable residual disease in multiple myeloma by multiparametric flow cytometry: Current paradigm, guidelines, and future applications

Evaluation of measurable residual disease in multiple myeloma by multiparametric flow cytometry: Current paradigm, guidelines, and future applications

Flow cytometric myeloma measurable residual disease testing in the era of targeted therapies

The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of multiple myeloma

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