Targeted Therapy Drugs: Daratumumab

Targeted Therapy Drugs: Daratumumab-Introduction

Daratumumab, jointly developed by Genmab along with the Johnson & Johnson subsidiary Janssen Biotech, by bingding to CD38 is the first monoclonal antibody approved for the treatment of multiple myeloma. It is administered as a single agent for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy, including a proteasome inhibitor (PI) and an immunomodulatory agent, or who are double-refractory to a PI and an immunomodulatory agent..

Targeted Therapy Drugs: Daratumumab-Target

The target of this drug is CD38. CD38 is a 46-kDa type II transmembrane glycoprotein with a short 20-aa N-terminal cytoplasmic tail and a long 256-aa extracellular domain. Functions ascribed to CD38 include receptor-mediated adhesion and signaling events, as well as important bifunctional ectoenzymatic activities that contribute to intracellular calcium mobilization. Under normal conditions, CD38 is expressed at relatively low levels on lymphoid and myeloid cells and in some tissues of nonhematopoietic origin. The relatively high expression of CD38 on all malignant cells in multiple myeloma in combination with its role in cell signaling suggest CD38 as a potential therapeutic Ab target for the treatment of multiple myeloid.

Targeted Therapy Drugs: Daratumumab-Disease

Daratumumab is applied for treating multiple myeloid. Multiple myeloma is a neoplasm that results in the accumulation of monoclonal plasma cells, predominantly in the bone marrow, which interfere with the production of normal white blood cells, red blood cells and platelets. It is the second most common hematological cancer after lymphoma, with an estimated incidence rate of 8 per 100,000 people and an estimated mortality rate of 2.2 per 100,000 people in Europe in 2012. Multiple myeloma remains largely incurable using current treatment approaches with fewer than 50% of patients surviving five years after diagnosis. Therefore, new approaches that induce long-term tumor regression and improve disease outcome are needed and urgently sought for.

Targeted Therapy Drugs: Daratumumab-Efficacy

The safety and efficacy of Daratumumab were demonstrated in two open-label studies. In one study of 106 participants receiving Daratumumab, 29 percent of patients experienced a complete or partial reduction in their tumor burden, which lasted for an average of 7.4 months. In the second study of 42 participants receiving Daratumumab, 36 percent had a complete or partial reduction in their tumor burden.

Targeted Therapy Drugs: Daratumumab-Side Effect

The most common side effects of Daratumumab were infusion-related reactions, fatigue, nausea, back pain, fever and cough. Daratumumab may also result in low counts of infection-fighting white blood cells (lymphopenia, neutropenia, and leukopenia) or red blood cells (anemia) and low levels of blood platelets (thrombocytopenia).

Targeted Therapy Drugs: Daratumumab-Reference

De Weers M, Tai Y T, van der Veer M S, et al. Daratumumab, a novel therapeutic human CD38 monoclonal antibody, induces killing of multiple myeloma and other hematological tumors[J]. The Journal of Immunology, 2011, 186(3): 1840-1848.

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