| Cycle length: 28 days. |
| Drug | Dose and route | Administration | Given on days |
| Daratumumab-hyaluronidase* | 1800 mg daratumumab plus 30,000 units hyaluronidase SC | Infuse SC into the abdominal wall over approximately 3 to 5 minutes. | Cycles 1 to 2: Days 1, 8, 15, and 22 Cycles 3 to 6: Days 1 and 15 Cycles 7 and beyond: Day 1 only |
| Lenalidomide¶ | 25 mgΔ by mouth | Administer with water. Swallow capsule whole; do not break, open, or chew. | All cycles: Take once daily on days 1 through 21 |
| Dexamethasone | 20 mg IV (first dose of the first cycle only) or by mouth (all other doses)∆◊ | Take with food (after meals or with food or milk) in the morning. | Cycles 1 to 2: Take once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 Cycles 3 to 6: Take once daily on days 1, 2, 15, and 16 Cycle 7 and beyond: Take once daily on days 1 and 2 |
| Dexamethasone | 40 mg∆ by mouth | Take with food (after meals or with food or milk) in the morning. | Cycles 3 to 6: Take once daily on days 8 and 22 Cycle 7 and beyond: Take once daily on days 8, 15, and 22 |
| Pretreatment considerations: |
| Emesis risk | - LOW.
- Refer to UpToDate topic on "Prevention and treatment of chemotherapy-induced nausea and vomiting in adults".
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| Prophylaxis for infusion reactions | - Premedicate with acetaminophen (650 to 1000 mg), diphenhydramine (25 to 50 mg), and dexamethasone (or equivalent glucocorticoid) one to three hours prior to each daratumumab infusion.[1,3] Observe all patients for at least six hours after the first infusion of daratumumab for evidence of infusion-related reactions.[2] To reduce the risk of delayed infusion reactions, administer oral glucocorticoids (eg, methylprednisolone 20 mg daily) to all patients for two days following each daratumumab infusion. If no major infusion reaction occurs during the first three infusions, may discontinue post-treatment glucocorticoids.[2,3] For patients with a history of asthma or COPD, one may add short- and long-acting bronchodilators and inhaled corticosteroids postinfusion. Discontinue these additional inhaled medications if no major infusion reactions occur during the first four infusions.[2,3]
- Refer to UpToDate topic on "Infusion-related reactions to therapeutic monoclonal antibodies used for cancer therapy".
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| Infection prophylaxis | - Daratumumab may be associated with an increased risk of herpes zoster. Antiviral prophylaxis (eg, acyclovir) is initiated within one week after starting daratumumab and continued for three months following treatment.[3] Primary prophylaxis with hematopoietic growth factors is not indicated. The risk of febrile neutropenia with this regimen was 5.7% in one clinical trial.[1]
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| Antithrombotic prophylaxis | - Routine antithrombotic prophylaxis with aspirin or low-molecular heparin is warranted. Thromboembolism was reported in 1.8% of patients in a clinical trial despite antithrombotic prophylaxis.[1] The risk of thromboembolism was 10% with another lenalidomide and high-dose dexamethasone-containing (RD) regimen.[4]
- Refer to UpToDate topic on "Thrombotic complications following treatment of multiple myeloma with immunomodulatory drugs (thalidomide, lenalidomide, and pomalidomide)".
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| Dose adjustment for baseline liver or renal dysfunction | - Patients with renal insufficiency experience more neutropenia with the use of lenalidomide.[5] Dose adjustment is recommended for patients with CrCl <60 mL/min.[6]
- Refer to UpToDate topic on "Chemotherapy nephrotoxicity and dose modification in patients with renal insufficiency: Conventional cytotoxic agents".
- Studies of lenalidomide have not been conducted in patients with hepatic impairment.
|
| Blood bank issues | - Notify blood transfusion centers of potential interference with cross-matching and red blood cell antibody screening and inform blood banks that a patient has received daratumumab. Type and screen patients prior to starting daratumumab.[3] Interference with testing may persist for up to six months after the last daratumumab infusion.
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| Monitoring parameters: |
- Assess CBC with differential, electrolytes, renal function, liver function, and M-protein level prior to starting each new cycle.
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| Suggested dose modifications for toxicity: |
| Hematologic toxicity | - A cycle of DRd should not be started unless the ANC is ≥1000/microL and the platelet count is ≥30,000/microL. DRd may be resumed following recovery. If a cycle of DRd is delayed because of neutropenia or thrombocytopenia, decrease the dose of lenalidomide to 15 mg when chemotherapy resumes. For subsequent cycles, reduce the lenalidomide dose by an additional 5 mg for each time the cycle is delayed by hematologic toxicity. There are no dose reductions for intracycle hematologic toxicity.
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| Other nonhematologic toxicity | - For grade 3 or 4 nonhematologic toxicity thought to be due to lenalidomide alone, hold DRd and restart DRd with lenalidomide at a reduced dose (5 mg less than previous dose) when toxicity has resolved to grade 2 or less.[6]
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| Infusion reactions | - In addition to more typical reactions, daratumumab-associated infusion reactions may mimic allergic rhinitis (eg, cough, wheezing, nasal congestion). Immediately interrupt daratumumab infusion for reaction of any severity. Manage symptoms as clinically appropriate.[3] For mild reactions that occur after the patient reaches home, acetaminophen or diphenhydramine are sufficient. Patients should contact their health care provider if shortness of breath or more significant reactions occur at home. For anaphylactic reaction or life-threatening administration-related reactions, immediately and permanently discontinue.[3]
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| If there is a change in body weight of at least 10%, doses should be recalculated. |
