Darzalex

Daratumumab instructions
Common name: Daratumumab
Trade name: Darzalex
All names: Daratumumab, Megaco, Daratumumab, Daratumumab, Darzalex

Indications:
Relapsed or refractory multiple myeloma

Usage and Dosage:
Generally, adults receive 16 mg/kg as an intravenous infusion at the following dosing intervals of Dalatumumab (genetic recombination).
In case of combined use of lenalidomide and dexamethasone:
weekly intervals (1 to 8 weeks), 2-week intervals (9 to 24 weeks) and 4-week intervals (after week 25)
In case of combined use of bortezomib and dexamethasone:
weekly intervals (1 to 9 weeks), 3-week intervals (10 to 24 weeks) and 4-week intervals (after 25th week) After 5 weeks)

Adverse reactions:
Common adverse reactions:
Tiredness, nausea, diarrhea, lack of breathing, fever, cough, muscle cramps, back or joint pain, chest pain
Cold-like symptoms (upper respiratory tract infection), nerve damage causing tingling, numbness or cramping pain, swelling of hands, ankles or feet
p>Other adverse effects:
Constipation, high blood pressure, muscle cramps, lung infection (pneumonia), a buildup of fluid in the lungs that makes you short of breath
Airway infection (such as the nose, sinuses, or throat), low number of red blood cells that carry oxygen in the blood (anemia), low number of white blood cells that help fight infection (neutropenia, lymphopenia), Decreased number of platelets, affecting coagulation function (thrombocytopenia), irregular heartbeat (atrial fibrillation), hepatitis, herpes, rash, itching, redness of the skin or redness and pain at the injection site, loss of appetite

Contraindications:
This product is contraindicated in patients with hypersensitivity to the active ingredients or any excipients of this product.

Notes:
Common and serious infusion reactions: If you have an infusion reaction, you can temporarily stop the infusion or stop treatment with DARZALEX completely.
Changes in Blood Tests: DARZALEX can affect blood type test results, and these changes will continue for 6 months after you stop using DARZALEX. Before you start treatment with DARZALEX, your doctor will test your blood type. Before you receive a blood transfusion, you should tell your doctor that you are receiving DARZALEX.
Reduced Blood Cell Count: DARZALEX reduces the number of white blood cells and platelets, which help fight infection and affect blood clotting. If you develop symptoms of fever, bruising, or bleeding, seek medical attention immediately.
Allergic reaction: rash, itching or hives, shortness of breath, wheezing or difficulty breathing, swelling of the face, lips, tongue or other parts of the body
Get medical help right away if you have any of the following symptoms: Chills, tiredness, shortness of breath or difficulty breathing, dizziness or lightheadedness (low blood pressure), cough, sore throat, Wheezing, tightness in throat, runny or stuffy nose, headache, itching, nausea, vomiting, chills, fever, neutropenia

Storage:
Unopened vials: should be stored in the refrigerator (2°C to 8°C), frozen, in original packaging protected from light.

Mechanism of action:
CD38 is a transmembrane glycoprotein (48kDa) expressed on the surface of hematopoietic cells, including multiple myeloma and other cell types and tissues, and has a variety of functions, such as receptor-mediated adhesion, signaling, and regulation of cyclase and hydrolase activities. Daratumumab is an IgG1κ human monoclonal antibody (mAb) that binds to CD38 and inhibits the growth of CD38-expressing tumor cells by inducing apoptosis directly through Fc-mediated cross-linking as well as through immune-mediated tumor cell lysis through complement-dependent cytotoxicity (CDC), antibody-dependent cell-mediated cytotoxicity (ADCC), and antibody-dependent cellular phagocytosis (ADCP). Myeloid-derived suppressor cells (MDSCs) and regulatory T cells express CD38 and are a subset susceptible to daratumumab-mediated cytolysis (CD38+ Tregs).

Safety and Efficacy:
Daratumumab was accelerated approval as a single agent in November 2015 for the treatment of multiple myeloma patients who have received at least three treatments, including a protease inhibitor (PI) and an immunomodulator, or a dual poorly soluble PI and an immunomodulator.
The current approval is based on two randomized, open-label trials in which daratumumab was added to standard treatment. The POLLUX trial (also known as MMY3003) showed a significant improvement in progression-free survival (PFS) when adding daratumumab to lenalidomide and dexamethasone compared with lenalidomide and dexamethasone alone.
The estimated median PFS was not reached in the Daratumumab arm compared with 18.4 months in the control arm (HR=0.37; 95% CI: 0.27, 0.52; p < 0.0001).
Similar results were also observed in the CASTOR trial (also known as MMY3004), which compared daratumumab, bortezomib, and dexamethasone with the combination of bortezomib and dexamethasone. Median PFS was not reached in the daratumumab arm compared with 7.2 months in the control arm (HR=0.39; 95% CI: 0.28, 0.53; p < 0.0001).