Darzalex SC

Adults w/ multiple myeloma in combination w/ bortezomib, lenalidomide, & dexamethasone for induction & consolidation in newly diagnosed patients eligible for autologous stem cell transplant (ASCT); w/ bortezomib, melphalan & prednisone in newly diagnosed patients ineligible for ASCT; w/ lenalidomide & dexamethasone in newly diagnosed patients ineligible for ASCT & w/ relapsed or refractory multiple myeloma who have received at least 1 prior therapy; w/ bortezomib, thalidomide, & dexamethasone in newly diagnosed patients eligible for ASCT; w/ bortezomib & dexamethasone in patients who have received at least 1 prior therapy; w/ pomalidomide & dexamethasone in patients who have received at least 1 prior line of therapy including lenalidomide & proteasome inhibitor; w/ carfilzomib & dexamethasone in patients w/ relapsed or refractory multiple myeloma who have received 1-3 prior lines of therapy; as monotherapy in patients who have received at least 3 prior lines of therapy including proteasome inhibitor & immunomodulatory agent or who are double-refractory to proteasome inhibitor & immunomodulatory agent. In combination w/ bortezomib, cyclophosphamide & dexamethasone in adults w/ newly diagnosed light chain amyloidosis.

Premed (administer 1-3 hr before each Darzalex SC dose): Acetaminophen 650-1,000 mg orally, diphenhydramine 25-50 mg (or equiv) orally or IV, long- or intermediate-acting corticosteroid. Monotherapy: Methylprednisolone 100 mg (or equiv) orally or IV, consider reducing dose to 60 mg (or equiv) following 2nd dose of Darzalex SC. Combination therapy: Dexamethasone 20 mg (or equiv) orally or IV prior to every Darzalex SC. Post-medication: Monotherapy: Methylprednisolone 20 mg (or equiv intermediate- or long-acting corticosteroid) orally for 2 days starting the day after Darzalex SC dose. Combination therapy: Oral methylprednisolone at dose ≤20 mg (or equiv intermediate- or long-acting corticosteroid) on the day after Darzalex SC. If background regimen-specific corticosteroid (eg, dexamethasone, prednisone) is administered the day after administration of Darzalex SC, additional corticosteroids may not be needed. Prophylaxis of herpes zoster reactivation: Initiate antiviral prophylaxis w/in 1 wk after starting Darzalex SC & continue for 3 mth following end of treatment. SC Recommended dose: 1,800 mg/30,000 u over approx 3-5 min. Multiple myeloma: Monotherapy & in combination w/ lenalidomide, pomalidomide or carfilzomib, & dexamethasone (4-wk cycle) Dosing schedule: Wk 1-8: Wkly (total of 8 doses). Wk 9-24: Every 2 wk, 1st dose to be given at wk 9 (total of 8 doses). Wk 25 onwards until disease progression: Every 4 wk, 1st dose to be given at wk 25. Combination w/ bortezomib, melphalan & prednisone (6-wk cycle) Dosing schedule: Wk 1-6: Wkly (total of 6 doses). Wk 7-54: Every 3 wk, 1st dose to be given at wk 7 (total of 16 doses). Wk 55 onwards until disease progression: Every 4 wk, 1st dose to be given at wk 55. Combination w/ bortezomib, thalidomide or lenalidomide, & dexamethasone (4-wk cycle) Dosing schedule: Induction phase: Wk 1-8: Wkly (total of 8 doses). Wk 9-16: Every 2 wk, 1st dose to be given at wk 9 (total of 4 doses). Stop for high dose chemotherapy & ASCT. Consolidation phase: Wk 1-8: Every 2 wk, 1st dose to be given at wk 1 upon treatment re-initiation following ASCT (total of 4 doses). Combination w/ bortezomib & dexamethasone (3-wk cycle) Dosing schedule: Wk 1-9: Wkly (total of 9 doses). Wk 10-24: Every 3 wk, 1st dose to be given at wk 10 (total of 5 doses). Wk 25 onwards until disease progression: Every 4 wk, 1st dose to be given at wk 25. Light chain amyloidosis in combination w/ bortezomib, cyclophosphamide & dexamethasone (4-wk cycle) Dosing schedule: Wk 1-8: Wkly (total of 8 doses). Wk 9-24: Every 2 wk, 1st dose to be given at wk 9 (total of 8 doses). Wk 25 onwards until disease progression or max of 2 yr: Every 4 wk, 1st dose to be given at wk 25.

History of severe hypersensitivity.

Not to be administered as IV. Not indicated & recommended for light chain amyloidosis w/ NYHA class IIIB or IV cardiac disease or Mayo Stage IIIB outside of controlled clinical trials. Immediately & permanently discontinue therapy in anaphylactic reaction or life-threatening (Grade 4) administration-related reactions. Interrupt treatment if ocular symptoms occur & seek immediate ophth eval prior to restarting treatment. Consider withholding treatment until recovery of neutrophils & platelets. Suspend treatment in patients who develop HBV reactivation. Severe reactions including hypoxia, dyspnea, HTN, tachycardia & ocular adverse reactions including choroidal effusion, acute myopia & acute angle closure glaucoma. Systemic administration-related reactions including resp symptoms (eg, bronchospasm, nasal congestion, cough, throat irritation, allergic rhinitis, wheezing), anaphylactic reaction, pyrexia, chest pain, pruritus, chills, vomiting, nausea, hypotension & blurred vision; severe or life-threatening & local inj-site reactions. Serious & fatal cardiac disorders in patients w/ light chain amyloidosis. May increase neutropenia & thrombocytopenia induced by background therapy. Patients w/ NYHA class IIIA or Mayo stage IIIA. Low body wt patients. Consider post-infusion medications including short- & long-acting bronchodilators & inhaled corticosteroids in patients w/ history of COPD. Premed w/ histamine-1 receptor antagonist, acetaminophen & corticosteroids. Periodically monitor CBC during treatment. Monitor patients w/ cardiac involvement of light chain amyloidosis; for cardiac adverse reactions; neutropenia for signs of infection; for clinical & lab signs of HBV reactivation during & for at least 6 mth following end of treatment. Type & screen patients prior to therapy. Perform HBV screening before treatment initiation. +ve result in indirect Coombs test. Interference w/ determination of complete response & disease progression in some treated patients w/ IgG kappa myeloma protein. May affect ability to drive & use machines due to fatigue. Females of reproductive potential must use effective contraception during treatment & 3 mth after the last dose. Contraindicated in pregnancy & not to breastfeed in combination w/ lenalidomide, thalidomide & pomalidomide. Potential risk to fetus. Defer administering live vaccines to neonates & infants exposed in utero until hematology evaluation is completed. Ped patients.

Peripheral & peripheral sensory neuropathy, paraesthesia, dizziness, headache; fatigue, edema, pyrexia, peripheral edema, infusion & inj site reactions, chills; URTI, pneumonia, bronchitis, UTI; constipation, diarrhea, nausea, abdominal pain, vomiting; musculoskeletal, musculoskeletal chest & back pain, muscle spasms, arthralgia; insomnia; rash, pruritus; hepatotoxicity; cough, dyspnea; decreased appetite, hyperglycemia, hypocalcemia; HTN, hypotension; arrhythmia; decreased platelets, lymphocytes, leukocytes, neutrophils & Hb; increased ALT & alkaline phosphatase, decreased Na, K & corrected Ca.

Interference w/ indirect antiglobulin tests (indirect Coombs test). False +ve assay results in serum protein electrophoresis & immunofixation tests.

Targeted Cancer Therapy

L01FC01 - daratumumab ; Belongs to the class of CD38 (Clusters of Differentiation 38) inhibitors. Used in the treatment of cancer.

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