Daratumumab Mechanism of Action:
Daratumumab is a human monoclonal antibody. It is indicated for the treatment of Multiple Myeloma in the following situations:
In Combination With … | Daratumumab Indications |
| Lenalidomide + dexamethasone | Newly diagnosed Multiple Myeloma patients ineligible for autologous stem cell transplant OR Patients with relapsed or refractory multiple myeloma who have received at least one prior therapy |
| Bortezomib, melphalan, and prednisone | Newly diagnosed Multiple Myeloma patients ineligible for autologous stem cell transplant |
| Bortezomib, thalidomide, and dexamethasone | Newly diagnosed Multiple Myeloma patients eligible for autologous stem cell transplant |
| Bortezomib and dexamethasone | Multiple Myeloma Patients who have received at least one prior therapy |
| Carfilzomib and dexamethasone | Patients with relapsed or refractory multiple myeloma who have received one to three prior lines of therapy |
| Pomalidomide and dexamethasone | Multiple Myeloma Patients who have received at least two prior therapies including lenalidomide and a proteasome inhibitor |
| As monotherapy | Multiple Myeloma Patients who have received at least three prior lines of therapy including a proteasome inhibitor and an immunomodulatory agent |
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Daratumumab Mechanism of Action:
Daratumumab is an IgG1κ human monoclonal antibody (mAb) that binds selectively to CD38 receptors.
CD 38 receptors are highly expressed on the Myeloma Cells (Plasma Cells) surface. CD 38 is also expressed on the surface of other hematopoietic and non-hematopoietic cells.
CD 38 receptor signaling is involved in the following processes:
- facilitating cell adhesion,
- transmitting signals between cells, and
- regulating certain enzyme activities involved in cellular processes
What happens when Daratumumab binds to CD 38 positive myeloma cells?
Daratumumab (Darzalex) induces apoptosis or programmed cell death, directly within the tumor cells by cross-linking of cells through the Fc region of the antibody.
Secondly, Darzalex also stimulates the immune system to attack and destroy the CD38-expressing tumor cells. This immune-mediated destruction occurs through mechanisms such as complement-dependent cytotoxicity (CDC), antibody-dependent cell-mediated cytotoxicity (ADCC), and antibody-dependent cellular phagocytosis (ADCP).
Furthermore, daratumumab has been observed to reduce the population of certain immune cells that contribute to tumor growth and immune suppression.
These include:
- Myeloid-derived suppressor cells (CD38+MDSCs),
- Regulatory T cells (CD38+Tregs), and
- Regulatory B cells (CD38+Bregs).
Daratumumab MOA Summarized:
In essence, daratumumab is a targeted therapy that specifically binds to CD38, impeding the growth of CD38-expressing tumor cells through direct induction of apoptosis and immune-mediated destruction.
Additionally, it modulates the immune response by reducing the presence of immune cells associated with tumor promotion and suppression.
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