What is the significance of the CD38 (Cluster of Differentiation 38) marker?

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Last updated: May 7, 2025 • View editorial policy

From the Guidelines

Daratumumab, an anti-CD38 monoclonal antibody, is the most effective treatment option for multiple myeloma, with an overall response rate of 29.2% and a median duration of response of 7.4 months, as seen in a phase I/II study 1.

CD38 Marker Importance

CD38 is a crucial cell surface marker found on various immune cells, particularly plasma cells, and is used in diagnosing and monitoring multiple myeloma and other hematological disorders.

  • CD38 is a transmembrane glycoprotein that functions as both a receptor and an enzyme involved in calcium signaling and cell adhesion.
  • In multiple myeloma, CD38 is highly expressed on malignant plasma cells, making it an excellent diagnostic marker and therapeutic target.

Treatment Options

  • Daratumumab (Darzalex) is an FDA-approved anti-CD38 monoclonal antibody used to treat multiple myeloma, typically administered intravenously at doses determined by body weight 1.
  • CD38 expression is also found on normal lymphocytes, monocytes, and NK cells, which can cause interference in flow cytometry analysis after anti-CD38 therapy.

Laboratory Testing

  • For laboratory testing, CD38 is commonly used in flow cytometry panels alongside other markers like CD138, CD56, and CD19 to identify abnormal plasma cells.
  • The high expression of CD38 on malignant cells compared to normal cells provides a therapeutic window that allows targeted treatment while minimizing damage to healthy tissues.

Adverse Events

  • Adverse events reported with daratumumab include fatigue, anemia, nausea, and thrombocytopenia, with grade 1 and 2 infusion-related reactions seen in 42.5% of patients, mainly during the first infusion 1.

Recommendation

Based on the most recent and highest quality study, daratumumab is the recommended treatment option for multiple myeloma, due to its efficacy and manageable adverse event profile 1.

From the FDA Drug Label

CD38 is a transmembrane glycoprotein (48 kDa) expressed on the surface of hematopoietic cells, including multiple myeloma and other cell types and tissues and has multiple functions, such as receptor mediated adhesion, signaling, and modulation of cyclase and hydrolase activity Daratumumab is an IgG1κ human monoclonal antibody (mAb) that binds to CD38 and inhibits the growth of CD38 expressing tumor cells by inducing apoptosis directly through Fc mediated cross linking as well as by immune-mediated tumor cell lysis through complement dependent cytotoxicity (CDC), antibody dependent cell mediated cytotoxicity (ADCC) and antibody dependent cellular phagocytosis (ADCP)

The CD38 marker is a target for daratumumab, which is a human monoclonal antibody that binds to CD38 and inhibits the growth of CD38 expressing tumor cells.

  • The CD38 marker is expressed on the surface of hematopoietic cells, including multiple myeloma and other cell types and tissues.
  • Daratumumab binds to CD38 and induces apoptosis and immune-mediated tumor cell lysis [2] [3].

From the Research

CD38 Marker Overview

  • CD38 is a transmembrane glycoprotein that is highly expressed on the surface of plasma cells, making it an ideal target for the treatment of multiple myeloma (MM) 4, 5.
  • CD38-targeting antibodies, such as daratumumab and isatuximab, have shown significant clinical efficacy in treating MM, with response rates of up to 30% in heavily pre-treated patients 4, 5.

Mechanism of Action

  • CD38-targeting antibodies work through a pleiotropic mechanism of action, including Fc-dependent effector mechanisms and immunomodulatory activities 5.
  • These antibodies can also deplete immunosuppressive cell populations, such as regulatory T cells and myeloid-derived suppressor cells, which can contribute to their anti-tumor effects 6.

Clinical Experience

  • Daratumumab is already approved as a monotherapy and in combination with other agents, such as lenalidomide and dexamethasone, for the treatment of relapsed MM 4, 5.
  • CD38-targeting antibodies have also shown promise in other hematological malignancies, such as acute lymphoblastic leukemia and acute myeloid leukemia, as well as in solid tumors 7, 6.
  • However, patients who develop resistance to CD38-targeting antibodies have a poor prognosis, with a median overall survival of approximately 8.6 months 8.

Re-Treatment with CD38-Targeting Antibodies

  • Re-treatment with CD38-targeting antibodies after a period of time off therapy may be effective in some patients, particularly those who have not developed resistance to these agents 7.
  • However, the clinical benefit of re-treatment is generally short-lived, and alternative therapies, such as chimeric antigen receptor T-cell therapy, may be needed to achieve longer-term responses 7.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.