Daratumumab Combination Approved for Multiple Myeloma

Web Exclusives - FDA Approvals, News & Updates, In the News

On November 21, 2016, the U.S. Food and Drug Administration approved daratumumab (DARZALEX, Janssen Biotech, Inc.) 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.

Daratumumab was previously granted accelerated approval in November 2015 as monotherapy for 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.

The current approval was based on two randomized, open-label trials in which daratumumab was added to standard therapies. The POLLUX trial (also known as MMY3003), demonstrated substantial improvement in progression-free survival (PFS) when daratumumab was added to lenalidomide and dexamethasone compared with lenalidomide and dexamethasone alone. The estimated median PFS had not been reached in the daratumumab arm and was 18.4 months in the control arm (HR=0.37; 95% CI: 0.27, 0.52; p<0.0001), representing a 63% reduction in the risk of disease progression or death in patients treated with daratumumab.

Similar results were observed in the CASTOR trial (also known as MMY3004), which compared the combination of daratumumab, bortezomib, and dexamethasone with bortezomib and dexamethasone. The estimated median PFS was not reached in the daratumumab arm and was 7.2 months in the control arm (HR=0.39; 95% CI: 0.28, 0.53; p<0.0001), representing a 61% reduction in the risk of disease progression or death for patients treated with daratumumab.

The most frequently reported adverse reactions (greater than or equal to 20%) in MMY3003 were infusion reactions, diarrhea, nausea, fatigue, pyrexia, upper respiratory tract infection, muscle spasm, cough and dyspnea. The most frequently reported adverse reactions (greater than or equal to 20%) in MMY3004 were infusion reactions, diarrhea, peripheral edema, upper respiratory tract infection, peripheral sensory Neutropenia and thrombocytopenia have been added to the Warnings and Precautions of the DARZALEX label.

The recommended dose of daratumumab is 16 mg/kg intravenously (calculated on actual body weight).

FDA granted daratumumab breakthrough therapy and orphan drug designation, as well as priority review. The current approval was granted three months prior to the PDUFA date of February 17, 2017. A description of these expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions—Drugs and Biologics, available at: http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm358301.pdf.

Full prescribing information is available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/761036s004lbl.pdf

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System by completing a form online at http://www.fda.gov/medwatch/report.htm, by faxing (1-800-FDA-0178) or mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).

US Food and Drug Administration. Daratumumab (darzalex). Updated November 22, 2016.

Related Items
First Chemoimmunotherapy Regimen Granted Accelerated Approval for Patients with Previously Treated DLBCL
Yvette Florio Lane
Web Exclusives published on June 12, 2019 in FDA Approvals, News & Updates, In the News
Welcome to the Fourth Annual Oncology Guide to New FDA Approvals
2019 Fourth Annual Oncology Guide to New FDA Approvals published on June 5, 2019 in FDA Approvals, News & Updates
New Indications Approved by the FDA in 2018 for Oncology Drugs
Dalia Buffery, MA, ABD
2019 Fourth Annual Oncology Guide to New FDA Approvals published on June 5, 2019 in FDA Approvals, News & Updates
FDA Approvals of Novel Brand-Name Prescription Cancer Drugs in 2018
2019 Fourth Annual Oncology Guide to New FDA Approvals published on June 5, 2019 in FDA Approvals, News & Updates
Braftovi (Encorafenib) plus Mektovi (Binimetinib) Third BRAF/MEK Inhibition Combination Approved for Metastatic Melanoma with BRAF Mutation
Lisa A. Raedler, PhD, RPh, Medical Writer
2019 Fourth Annual Oncology Guide to New FDA Approvals published on June 5, 2019 in FDA Approvals, News & Updates, Melanoma
Copiktra (Duvelisib) Approved for Relapsed or Refractory CLL, SLL, and Follicular Lymphoma
Lisa A. Raedler, PhD, RPh, Medical Writer
2019 Fourth Annual Oncology Guide to New FDA Approvals published on June 5, 2019 in FDA Approvals, News & Updates, Lymphoma
Daurismo (Glasdegib) Approved, in Combination with Low-Dose Cytarabine, for Newly Diagnosed Acute Myeloid Leukemia in Older Adults or Those Unfit for Intensive Chemotherapy
Loretta Fala, Medical Writer
2019 Fourth Annual Oncology Guide to New FDA Approvals published on June 5, 2019 in FDA Approvals, News & Updates, Leukemia
Erleada (Apalutamide) First Drug Approved by the FDA for Nonmetastatic Castration-Resistant Prostate Cancer
Loretta Fala, Medical Writer
2019 Fourth Annual Oncology Guide to New FDA Approvals published on June 5, 2019 in FDA Approvals, News & Updates, Prostate Cancer
Imbruvica (Ibrutinib) plus Rituxan (Rituximab) New Combination Approved for the Treatment of Waldenström’s Macroglobulinemia
Lisa A. Raedler, PhD, RPh, Medical Writer
2019 Fourth Annual Oncology Guide to New FDA Approvals published on June 5, 2019 in FDA Approvals, News & Updates, Lymphoma
Infugem (Gemcitabine) First Formulation of Premixed, Ready-to-Administer Intravenous Chemotherapy Approved for Several Tumor Types
Lisa A. Raedler, PhD, RPh, Medical Writer
2019 Fourth Annual Oncology Guide to New FDA Approvals published on June 5, 2019 in FDA Approvals, News & Updates
Last modified: February 19, 2019