Darzalex SC

Per 15 mL inj Daratumumab 1,800 mg, hyaluronidase-fihj 30,000 u

Adults w/ multiple myeloma in combination w/ bortezomib, melphalan & prednisone in newly diagnosed patients ineligible for autologous stem cell transplant (ASCT); in combination w/ lenalidomide & dexamethasone in newly diagnosed patients ineligible for ASCT & w/ relapsed or refractory multiple myeloma who have received at least 1 prior therapy; in combination w/ bortezomib, thalidomide & dexamethasone in newly diagnosed patients eligible for ASCT; in combination w/ bortezomib & dexamethasone in patients who have received at least 1 prior therapy; in combination w/ pomalidomide & dexamethasone in patients who have received at least 1 prior line of therapy including lenalidomide & proteasome inhibitor; in combination 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 dose): Acetaminophen 650-1,000 mg PO, diphenhydramine 25-50 mg (or equiv) PO or IV, long- or intermediate-acting corticosteroid. Monotherapy: Administer methylprednisolone 100 mg (or equiv) PO or IV, reduce dose to methylprednisolone 60 mg (or equiv) following 2nd dose of Darzalex SC; Combination therapy: Administer dexamethasone 20 mg (or equiv) PO or IV prior to every DARZALEX SC. Post-medication: Monotherapy: Administer methylprednisolone 20 mg (or equiv intermediate- or long-acting corticosteroid) PO 2 days starting the day after Darzalex SC dose; Combination therapy: Oral methylprednisolone at dose ≤20 mg (or equiv intermediate- or long-acting corticosteroid) starting 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. Monotherapy & 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 (total of 8 doses) (give 1st dose of every-2-wk schedule at wk 9). Wk 25 onwards until disease progression: Every 4 wk (give 1st dose of every-4-wk schedule 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 (total of 16 doses) (give 1st dose of every-3-wk schedule at wk 7). Wk 55 onwards until disease progression: Every 4 wk (give 1st dose of every-4-wk schedule at wk 55). Combination w/ bortezomib, thalidomide & dexamethasone (4-wk cycle) Dosing schedule: Induction phase: Wk 1-8: Wkly (total of 8 doses). Wk 9-16: Every 2 wk (total of 4 doses) (give 1st dose of every-2-wk schedule at wk 9). Stop for high dose chemotherapy & ASCT. Consolidation phase: Wk 1-8: Every 2 wk (total of 4 doses) (give 1st dose of every-2-wk schedule at wk 1 upon treatment re-initiation following ASCT). Combination w/ bortezomib & dexamethasone (3-wk cycle) Dosing schedule: Wk 1-9: Wkly (total of 9 doses). Wk 10-24: Every 3 wk (total of 5 doses) (give 1st dose of every-3-wk schedule at wk 10). Wk 25 onwards until disease progression: Every 4 wk (give 1st dose of every-4-wk schedule at wk 25). Light chain amyloidosis Combination w/ bortezomib, cyclophosphamide & dexamethasone (4-wk cycle): Dosing schedule: Wk 1-8: Wkly (total of 8 doses). Wk 9-24: Every 2 wk (total of 8 doses) (give 1st dose of every-2-wk schedule at wk 9). Wk 25 onwards until disease progression or max of 2 yr: Every 4 wk (give 1st dose of every-4-wk schedule at wk 25).

History of severe hypersensitivity.

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 administration-related reactions. Interrupt treatment if ocular symptoms occur. 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. May increase neutropenia & thrombocytopenia induced by background therapy. Patients w/ NYHA class IIIA or Mayo stage IIIA. Premed w/ histamine-1 receptor antagonist, acetaminophen & corticosteroids. Periodically monitor CBC during treatment. Monitor patients w/ cardiac involvement of light chain amyloidosis; neutropenia for signs of infection; 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 initiation of treatment. +ve result in indirect Coombs test. Interference w/ determination of complete response & disease progression in some treated patients w/ IgG kappa myeloma protein. 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.

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

Interference w/ indirect antiglobulin tests (indirect Coombs test). False +ve 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.

S