Daratumumab

Daratumumab is a human IgG1k monoclonal antibody (mAb) that binds with high affinity to the CD38 molecule, which is highly expressed on the surface of multiple myeloma cells.1 Daratumumab triggers a person’s own immune system to attack cancer cells, resulting in rapid tumor cell death through multiple immune-mediated mechanisms of action and through immunomodulatory effects, in addition to direct tumor cell death via apoptosis (programmed cell death).1,2,3,4,5 Daratumumab is being developed by Janssen Biotech, Inc. under an exclusive worldwide license to develop, manufacture and commercialize daratumumab from Genmab.

Marketed Indications and Safety
Daratumumab, marketed as DARZALEX®, is the first human CD38 monoclonal antibody to reach the market and the first monoclonal antibody (mAb) to receive U.S. Food and Drug Administration (U.S. FDA) approval to treat multiple myeloma.

DARZALEX (daratumumab) injection for intravenous infusion is indicated for the treatment of adult patients in the United States:

  • in combination with bortezomib, thalidomide and dexamethasone for the treatment of patients with newly diagnosed multiple myeloma who are eligible for autologous stem cell transplant (ASCT);
  • in combination with lenalidomide and dexamethasone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for ASCT; 
  • in combination with bortezomib, melphalan and prednisone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for ASCT;
  • in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of patients with multiple myeloma who have received at least one prior therapy;
  • in combination with pomalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor (PI);
  • and as a monotherapy for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy, including a PI and an immunomodulatory agent, or who are double-refractory to a PI and an immunomodulatory agent.

DARZALEX is indicated in Europe:

  • for use in combination with bortezomib, thalidomide and dexamethasone for the treatment of adult patients with newly diagnosed multiple myeloma who are eligible for ASCT;
  • for use in combination with bortezomib, melphalan and prednisone for the treatment of adult patients with newly diagnosed multiple myeloma who are ineligible for ASCT; 
  • for use in combination with lenalidomide and dexamethasone as treatment for adult patients with newly diagnosed multiple myeloma who are ineligible for ASCT; 
  • for use in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy;
  • and as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma, whose prior therapy included a PI and an immunomodulatory agent and who have demonstrated disease progression on the last therapy.

The option to split the first infusion of DARZALEX over two consecutive days has been approved in both Europe and the U.S.

DARZALEX is indicated in Japan:

  • for use in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for treatment of adults with relapsed or refractory multiple myeloma;
  • for use in combination with bortezomib, melphalan and prednisone for the treatment of patients with newly diagnosed multiple myeloma ineligible for ASCT

The warnings and precautions for DARZALEX include infusion reactions, interference with serological testing and interference with determination of complete response. The most frequently reported adverse reactions (incidence ≥20%) in clinical trials were: infusion reactions, neutropenia, thrombocytopenia, fatigue, nausea, diarrhea, constipation, vomiting, muscle spasms, arthralgia, back pain, pyrexia, chills, dizziness, insomnia, cough, dyspnea, peripheral edema, peripheral sensory neuropathy and upper respiratory tract infection. 

Please consult the full U.S. Prescribing information and the full European Summary of Product Characteristics for all the labeled safety information for DARZALEX.

Clinical Development
A comprehensive clinical development program for daratumumab is ongoing, including multiple Phase III studies in smoldering, frontline and relapsed and multiple myeloma settings and in amyloidosis.  Additional studies are ongoing or planned to assess the potential of daratumumab in other malignant  diseases, such as NKT-cell lymphoma and B-cell and T-cell acute lymphoblastic leukemia (ALL).  A subcutaneous formulation of daratumumab is being investigated for multiple myeloma and amyloidosis.

Breakthrough Therapy Designations
Daratumumab has received Fast Track Designation and two Breakthrough Therapy Designations from the US Food and Drug Administration (FDA) in specific types of multiple myeloma.   Breakthrough Therapy Designation is a program intended to expedite the development and review of drugs to treat serious or life-threatening diseases in cases where preliminary clinical evidence shows that the drug may provide substantial improvements over available therapy. Daratumumab has also received Orphan Drug Designation from the US FDA and the European Medicines Agency (EMA) for the treatment of multiple myeloma.

1 De Weers, M et al. Daratumumab, a Novel Therapeutic Human CD38 Monoclonal Antibody, Induces Killing of Multiple Myeloma and Other Hematological Tumors. The Journal of Immunology. 2011; 186: 1840-1848.
2 DARZALEX Prescribing information, May 2018. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/761036s013lbl.pdf Last accessed May 2018
3 Overdijk, MB, et al. Antibody-mediated phagocytosis contributes to the anti-tumor activity of the therapeutic antibody daratumumab in lymphoma and multiple myeloma. MAbs. 2015; 7: 311-21.
4Krejcik, MD et al. Daratumumab Depletes CD38+ Immune-regulatory Cells, Promotes T-cell Expansion, and Skews T-cell Repertoire in Multiple Myeloma. Blood. 2016; 128: 384-94.
5Jansen, JH  et al. Daratumumab, a human CD38 antibody induces apoptosis of myeloma tumor cells via Fc receptor-mediated crosslinking. Blood. 2012; 120(21): abstract 2974.

Back to top

Multiple myeloma is an incurable blood cancer that starts in the bone marrow and is characterized by an excess proliferation of plasma cells.1  While some patients with multiple myeloma have no symptoms at all, others are diagnosed due to symptoms which can include bone problems, low blood counts, calcium elevation, nervous system symptoms, kidney problems or infections.2 The 5-year survival rate for multiple myeloma patients is estimated at 50.7% in the U.S.3 It was expected that approximately 26,000 people would be newly diagnosed with multiple myeloma and approximately 13,650 people would die from the disease in the U.S. in 2018.4  It was estimated that approximately 160,000 people worldwide would be diagnosed with multiple myeloma and 106,000 would die from the disease in 2018.5

Daratumumab is indicated for certain multiple myeloma indications – click here for information.  Daratumumab is also being investigated in clinical studies for multiple myeloma. For more information on these studies, visit clinicaltrials.gov.


1American Cancer Society. "Multiple Myeloma Overview." Available at http://www.cancer.org/cancer/multiplemyeloma/detailedguide/multiple-myeloma-what-is-multiple-myeloma. Accessed August 2015.
2  American Cancer Society. "Signs and Symptoms of Multiple Myeloma." https://www.cancer.org/cancer/multiple-myeloma/detection-diagnosis-staging/signs-symptoms.html. Accessed August 2018.
3  Surveillance, Epidemiology and End Results Program (SEER). Cancer Stat Facts: Myeloma. Available at http://seer.cancer.gov/statfacts/ html/mulmy.html. Accessed December 2018 
Globocan 2018. United States of America Fact Sheet. Available at http://gco.iarc.fr/today/data/factsheets/populations/840-united-states-of-america-fact-sheets.pdf
5  Globocan 2018. World Fact Sheet. Available at http://gco.iarc.fr/today/data/factsheets/populations/900-world-fact-sheets.pdf. Accessed December 2018

Back to top

Natural killer / T-cell lymphoma (NKTCL), Nasal Type is a type of non-Hodgkin’s lymphoma, which is almost always associated with Epstein-Barr virus. Up to 75% of cases develop in the upper aerodigestive tract, most commonly in the nasal cavity. NKTCL is the most common type of peripheral T-cell lymphoma in many Asian countries, though disease incidence is still rare. The median age of presentation is 40 to 50 years old, but it may occur at any age. Early-stage localized nasal disease is highly curable with combination therapy, though the optimal treatment is as yet undefined.

Source:  http://www.cancernetwork.com/leukemia-lymphoma/current-management-nasal-nkt-cell-lymphoma

Back to top

Amyloidosis is a disease that occurs when amyloid proteins, which are abnormal proteins, accumulate in tissues and organs. When the amyloid proteins cluster together they form deposits which damages the tissues and organs. Amyloidosis most frequently affects the kidneys, heart, nervous system, liver and digestive tract. There is currently no cure for amyloidosis. It can be treated with chemotherapy, dexamethasone, stem cell transplants and supportive therapies1.  Approximately 12-15% of multiple myeloma patients will develop light chain amyloidosis (AL amyloidosis).2 It is estimated that around 4,000 people in the U.S. develop AL amyloidosis each year.2 It is estimated that approximately 6,900 people in the U.S. and the 5 major European markets are diagnosed with AL amyloidosis annually.3,4,5,6



1 Mayo Clinic website: www.mayoclinic.com/health/amyloidosis/DS00431
Cancer.Net Guide to Amyloidosis. https://www.cancer.net/cancer-types/amyloidosis/risk-factors Accessed December 2018.
3 RA Kyle, Blood 1992
4 UK National Amyloidosis Center. http://www.amyloidosis.org.uk
5 SEER US cancer statistics
6 Putnam Primary Research (June 2017)


Back to top