Formulation and Specifications: Injection: 100 mg (5 ml)/vial, 400 mg (20 ml)/vial
Indications: Monotherapy in adult patients with relapsed and refractory multiple myeloma who have received prior therapy including proteasome inhibitors and immunomodulators and whose disease progressed on the last treatment.
Key points for rational drug use:
1. Management of immediate infusion-related reactions: Daretuzumab is a biologic agent that, as an exogenous protein, has infusion-related reactions (IRRs), as do other targeted monoclonal antibodies. IRRs are mainly manifested as nasal congestion, cough, throat irritation, chills, nausea, and vomiting, with severe IRRs manifesting as bronchospasm, dyspnea, laryngeal edema, pulmonary edema, and hypertension. The prescribed infusion rate should be strictly adhered to when injecting daratumumab to reduce the risk of infusion-related reactions. For IRRs of any grade/severity, the infusion should be interrupted immediately and treated symptomatically. Daretuzumab IRR occurs predominantly after the first infusion in approximately 46%, with a median time to IRR of 1.5 hours and a 35% incidence of infusion interruption due to reactions. Daretuzumab can be stored at room temperature for 15 hours (including infusion time) after infusion interruption. After the symptoms of grade 1 to 2 (mild to moderate) infusion-related reactions have subsided, reinitiation of the infusion may be considered, but at a rate no greater than half the rate of infusion at the time of the IRR. If the patient does not experience any further IRR symptoms, the infusion rate may be continued in increments, depending on the clinical situation, up to a maximum rate of 200 ml/hr. After symptoms of Grade 3 (severe) infusion-related reactions have subsided, reinitiation of the infusion may be considered, but at a rate no greater than half the infusion rate at the time of the IRR. If the patient does not develop other symptoms, the infusion rate may be restarted in increments, with the increment and interval depending on the clinical situation. If Grade 3 symptoms occur again, the above steps should be repeated. The third occurrence of a grade ≥3 infusion-related reaction should result in permanent termination of treatment with this product. The occurrence of a grade 4 (life-threatening) IRR should permanently discontinue treatment with this product. The risk of IRR can be reduced by giving the following preinfusion medications to all patients 1 to 3 hours prior to each infusion of this product: (1) Glucocorticoids (long-acting or intermediate-acting): 100 mg of intravenous methylprednisolone or equivalent. After the second infusion, the glucocorticoid dose can be reduced (60 mg of methylprednisolone given orally or intravenously). (2) Antipyretic agents (oral acetaminophen 650-1000mg). (3) Antihistamines (Benadryl 25-50mg or equivalent given orally or intravenously).
2. Delayed infusion-related reactions: manifest as delayed fever. The risk of delayed infusion-related reactions can be reduced by giving oral glucocorticoids (20 mg methylprednisolone or equivalent doses of intermediate/long-acting glucocorticoids, depending on local standards) daily for 2 days after each infusion of this product (starting the day after the infusion). In addition, postinfusion medications including short- and long-acting bronchodilators and inhaled glucocorticoids should be considered for patients with a history of chronic obstructive pulmonary disease. After the first four infusions, these inhaled postinfusion medications may be discontinued at the discretion of the physician if the patient does not experience a significant IRR.
3. Impact on blood group determination and transfusion strategy: Daretuzumab can bind to CD38 antigen expressed at low levels on the surface of red blood cell membranes, causing false-positive indirect anti-human globulin tests during cross-matching and interfering with blood matching, which may persist up to 6 months after the last daretuzumab transfusion. Blood group determination and antibody screening should be completed before the patient begins daltezumab therapy. In the case of planned transfusions, the transfusion center should be notified of this interfering factor in the indirect antiglobulin test. Application of dithiothreitol to treat the red blood cells of the patient to be tested is one of the treatment methods. Erythrocyte genotyping is unaffected by daretuzumab and can be performed at any time.
4. Daretuzumab is myelosuppressive and requires careful monitoring of blood count after application.
5. Daretuzumab may cause an increased risk of herpes zoster infection, and reactivation of herpes zoster has been reported in approximately 3% of patients. Antiviral prophylaxis is recommended to prevent reactivation of herpes zoster virus, whether used alone or in combination with any other regimen.
6. Daretuzumab dose adjustment is not required in patients with concomitant hepatic or renal impairment.
7. There is a risk of hepatitis B virus reactivation in patients treated with this product. Screening for hepatitis B virus should be performed prior to treatment with daretuzumab, and hepatitis B virus carriers should be prophylactically treated with drugs that inhibit viral replication and monitored for viral load; in patients with hepatitis B virus reactivation during daretuzumab treatment, daretuzumab and any combination hormone or chemotherapy should be discontinued and appropriate therapy given. Patients with positive hepatitis B virus serologic test results should be monitored for clinical and laboratory indications of hepatitis B virus reactivation during treatment with this product and for at least 6 months after completion of treatment.
8. Other treatments: A phase III clinical trial of daltezumab in combination with dexamethasone and bortezomib in primary systemic mild chain amyloidosis is ongoing, with a significant increase in hematologic remission rates in the daltezumab-containing group compared to the control group in an interim analysis. Daretuzumab in combination with other agents has been approved in NCCN guidelines for the treatment of patients with refractory relapsed and primary multiple myeloma, including daretuzumab in combination with lenalidomide and dexamethasone for relapsed patients and older primary patients, daretuzumab in combination with bortezomib and dexamethasone for refractory relapsed patients, daretuzumab in combination with bortezomib, melphalan and prednisone acetate for older primary patients, and daretuzumab in combination with bortezomib, melphalan and prednisone acetate for older primary patients. Daretuzumab in combination with bortezomib, thalidomide and dexamethasone for young primary patients.