Patients eligible for transplant

Daratumumab granted approval for frontline use in Japan

On 22 August 2019, Genmab A/S (Nasdaq: GMAB) announced that the Ministry of Health, Labor and Welfare (MHLW) in Japan had approved the use of daratumumab in combination with bortezomib, melphalan and prednisone (VMP) for the treatment of patients with newly diagnosed multiple myeloma (MM) who are ineligible for autologous stem cell transplant (ASCT).1

The approval was based on data from the phase III ALCYONE study (NCT02195479) 2 which showed a 50% reduction in the risk of disease progression or death with daratumumab combined with VMP in newly diagnosed patients with MM who were ineligible for ASCT. The MM Hub previously reported the results of this trial when it was presented as a late-breaking abstract at the 2017 American Society of Hematology (ASH) Annual Meeting.  

Daratumumab is the first human CD38 monoclonal antibody (mAb) to reach the market in the United States, Europe, and Japan for the treatment of MM.3

Mechanism of action

Daratumumab is an IgG1κ mAb that has a high affinity for CD38, which is overexpressed on MM cells. Daratumumab induces MM cell death through various mechanisms including antibody-dependent cell-mediated cytotoxicity, complement-dependent cytotoxicity, antibody-dependent cellular phagocytosis and apoptosis.4

Daratumumab intravenous infusion is indicated for the treatment of adult patients with MM in the United States:5
  • In combination with lenalidomide and dexamethasone in newly diagnosed patients who are ineligible for ASCT and in patients with relapsed or refractory MM who have received at least one prior therapy
  • In combination with VMP in newly diagnosed patients who are ineligible for ASCT
  • In combination with bortezomib and dexamethasone in patients who have received at least one prior therapy
  • In combination with pomalidomide and dexamethasone in patients who have received at least two prior therapies including lenalidomide and a proteasome inhibitor (PI)
  • As monotherapy, in patients 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
Daratumumab intravenous infusion is indicated for the treatment of adult patients within Europe:5
  • In combination with VMP for the treatment of adult patients with newly diagnosed MM who are ineligible for ASCT
  • As monotherapy for the treatment of adult patients with relapsed and refractory MM, whose prior therapy included a PI and an immunomodulatory agent and who demonstrated disease progression on the last therapy
  • In combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of adult patients with MM who have received at least one prior therapy
Daratumumab is indicated in Japan:6
  • In combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of adults with relapsed or refractory MM
  • In combination with VMP for the treatment of patients with newly diagnosed MM ineligible for ASCT
References
  1. Genmab. Genmab Announces Approval of DARZALEX® (daratumumab) in Frontline Multiple Myeloma in Japan. https://ir.genmab.com/news-releases/news-release-details/genmab-announces-approval-darzalexr-daratumumab-frontline. Published August 22 2019 [Accessed August 22 2019]
  2. Clinicaltrials. A Study of Combination of Daratumumab and Velcade (Bortezomib) Melphalan-Prednisone (DVMP) Compared to Velcade Melphalan-Prednisone (VMP) in Participants With Previously Untreated Multiple Myeloma. https://clinicaltrials.gov/ct2/show/NCT02195479 [Accessed August 22 2019]
  3. Globenewswire. Genmab Announces Approval of DARZALEX® (daratumumab) in Frontline Multiple Myeloma in Japan. http://www.globenewswire.com/news-release/2019/08/22/1905188/0/en/Genmab-Announces-Approval-of-DARZALEX-daratumumab-in-Frontline-Multiple-Myeloma-in-Japan.html Published August 22 2019 [Accessed August 22 2019]
  4. European Medicines Agency. ANNEX I SUMMARY OF PRODUCT CHARACTERISTICS. https://www.ema.europa.eu/en/documents/product-information/darzalex-epar-product-information_en.pdf [Accessed August 22 2019]
  5. DARZALEX (daratumumab) Prescribing Information. June 2019. http://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/DARZALEX-pi.pdf. [Accessed August 23 2019]
  6. Genmab. Daratumumab. http://www.genmab.com/product-pipeline/products-in-development/daratumumab [Accessed August 23 2019]
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