Multiple myeloma, also called Kahler disease, myelomatosis, and plasma cell myeloma, is the second most common hematological cancer. It is a cancer of the plasma cells and it accounts for approximately 1% of all cancers. Although multiple myeloma is considered an incurable malignancy over the past decade significant progress has been made in treating the disease with novel immunomodulating agents such as lenalidomide, a thalidomide analogue (Revlimid?; Celgene) and bortezomib (Velcade?, Millennium Pharmaceuticals/Takeda Pharmaceutical)

The 5-year relative survival rate for multiple myeloma is around 40%. Based on currently available data, there is a strong unmet need – requiring ongoing research for new treatment modalities to improve the survival.

Recent data from the U.S. National Cancer Institute (NCI) estimates a total of 22,350 new cases and 10,710 deaths from multiple myeloma in the United States in 2013.

Risk factors
Studies have found that age is a risk factor in developing multiple myeloma. Most people are diagnosed after 65 years of age, but the disease is extremely rare in people younger than 35 years of age. Another risk factors is race. African Americans have the highest risk factor, while Asian Americans, on the other hand, have low incidence of the disease. The reason for this difference between racial groups is not known. Multiple myeloma is also diagnosed more in men than women. The NCI estimates that about 12,000 men and 10,000 women will be diagnosed with multiple myeloma in the United States in 2013. Studies have shown that a person’s risk of multiple myeloma may be higher if a close relative has had the disease.

Ongoing First-in-Human Dose-escalation Study of Daratumumab in Patients with Multiple Myeloma Show an Acceptable Safety Profile

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A personal history of Monoclonal Gammopathy of Undetermined Significance (MGUS), a benign condition in which abnormal plasma cells make M proteins, may lead to the development of multiple myeloma. MGUS is present in about 3% of persons >50 years and in 5% >70 years of age. The risk of progression to multiple myeloma or a related disorder is 1% per year. Generally, patients with MGUS have an M protein in the serum without findings of multiple myeloma, macroglobulinemia, amyloidosis, or lymphoma and have fewer than 10% of plasma cells in the bone marrow. [1]

Unmet need
Daratumumab (HuMax?-CD38; Genmab), is a human CD38 monoclonal antibody with broad-spectrum killing activity which effectively mediates killing of CD38-expressing tumor cells via antibody-dependent cell-mediated cytotoxicity, complement-dependent cytotoxicity and apoptosis. The trial drug is being tested against multiple myeloma. Researchers believe that the daratumumab may also have potential in a broad range of other hematological diseases on which CD38 is expressed, including diffuse large B-cell lymphoma, chronic lymphocytic leukemia, acute lymphoblastic leukemia, acute myeloid leukemia, follicular lymphoma and mantle cell lymphoma.

Regulatory Status
Daratumumab has received Fast Track Designation and Breakthrough Therapy Designation from the U.S. Food and Drug Administration (FDA) for the treatment of multiple myeloma patients who have relapsed after other therapies and have no further treatment options. The Breakthrough Therapy Designation program is intended to expedite the development and review of drugs to treat serious or life-threatening diseases.

Daratumumab is currently in development as single agent and in combination with other compounds.In vitro experiments have shown that daratumumab acts synergistically with novel agents such as lenalidomide and bortezomib to induce killing of multiple myeloma tumor cells. [1,2] The drug also helps to eradicate multiple myeloma tumor cells that were obtained from lenalidomide or bortezomib refractory patients.

A Phase I/II safety trial of daratumumab in relapsed/refractory multiple myeloma is ongoing and researchers are planning combination studies of daratumumab, with lenalidomide and dexamethasone, and with bortezomib and dexamethasone in relapsed multiple myeloma patients

Updated Research
During the 18th Congress of the European Hematology Association in Stockholm, being held from June 13-16, 2013 in the Stockholmsm?ssan (Stockholm International Fairs) in Stockholm, Sweden, researchers presented updated results from the ongoing GEN501 study aiming to recruit 78 heavily pretreated patients. The primary objective of this study is to establish the safety profile of daratumumab whereas main secondary objectives are to evaluate the efficacy of daratumumab and establish the maximum tolerated dose (MTD).

Commenting on the effectiveness of daratumumab, Henk Lokhorst, MD, University Medical Center Utrecht, The Netherlands noted: “To date daratumumab has been well tolerated with most common adverse events reported being infusion related reactions. At doses up to and including 2mg/kg the drug has shown promising efficacy with 31% of patients achieving a response and 67% of patients in dose cohorts 4 mg/kg and above achieving a response. This is currently unprecedented for any single-agent treatment of multiple myeloma.”

In this present ongoing first-in-human (FIH) dose-escalation study of daratumumab in patients with multiple myeloma, the safety profile has been acceptable and preliminary efficacy data have already been published [1,2].


[1] Kyle RA, Rajkumar SV: Monoclonal gammopathy of undetermined significance and smouldering multiple myeloma: emphasis on risk factors for progression. Br J Haematol 139 (5): 730-43, 2007
Clinica trials
[2] Van der Veer MS, De Weers M, Van Kessel B, Bakker JM, Wittebol S, Parren PWHI, Lokhorst HM, Mutis T. Improved Myeloma Targeting by Combination of the Human Anti-CD38 Antibody Daratumumab with Lenalidomide and Bortezomib. Blood (ASH Annual Meeting Abstracts) 2010 116: Abstract 3030

Clinical trials

NCT00574288– Daratumumab (HuMax?-CD38)Safety Study in Multiple Myeloma

EHA Congress:Daratumumab, a CD38 Monoclonal Antibody study in Advanced Multiple Myeloma – an open-lable, dose escalation followe by open-lable extension in a single-arm Phase I/II study (abstract S576)

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