Darzalex

Adults w/ multiple myeloma in combination w/ lenalidomide & dexamethasone in newly diagnosed patients ineligible for autologous stem cell transplant (ASCT) & w/ relapsed or refractory multiple myeloma who have received at least 1 prior therapy; w/ bortezomib, melphalan & prednisone in newly diagnosed patients ineligible for ASCT; 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/ carfilzomib & dexamethasone in patients w/ relapsed or refractory multiple myeloma who have received 1-3 prior lines of therapy; w/ pomalidomide & dexamethasone in patients who have received at least 2 prior therapies including lenalidomide & proteasome inhibitor; 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.

Pre-infusion medication (administer 1-3 hr before every Darzalex infusion): 650-1,000 mg acetaminophen orally, 25-50 mg diphenhydramine (or equiv) orally or IV, long- or intermediate-acting corticosteroid. Monotherapy: 100 mg methylprednisolone (or equiv) IV, consider reducing dose to 60 mg (or equiv) orally or IV following 2nd infusion. Combination therapy: 20 mg dexamethasone (or equiv) orally or IV. Post-infusion medication: Monotherapy: 20 mg methylprednisolone (or equiv dose of intermediate- or long-acting corticosteroid) orally for 2 days starting the day after Darzalex infusion. Combination therapy: Consider administering oral methylprednisolone ≤20 mg (or equiv dose of intermediate- or long-acting corticosteroid) starting the day after Darzalex infusion. If background regimen-specific corticosteroid (eg, dexamethasone, prednisone) is administered the day after Darzalex infusion, additional corticosteroids may not be needed. Prophylaxis of herpes zoster reactivation: Initiate antiviral prophylaxis w/in 1 wk after starting Darzalex & continue for 3 mth following end of treatment. IV infusion Combination w/ lenalidomide or pomalidomide (4-wk cycle) & low-dose dexamethasone, & monotherapy 16 mg/kg. 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 regimen) 16 mg/kg. 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 & dexamethasone (4-wk cycle regimen) 16 mg/kg. 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 re-initiation of treatment following ASCT (total of 4 doses). Combination w/ bortezomib & dexamethasone (3-wk cycle) 16 mg/kg. 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. Combination w/ carfilzomib & dexamethasone (4-wk cycle) Dosing schedule: Wk 1: 8 mg/kg on days 1 & 2 (total of 2 doses). Wk 2-8: 16 mg/kg wkly (total of 7 doses). Wk 9-24: 16 mg/kg every 2 wk, 1st dose to be given at wk 9 (total of 8 doses). Wk 25 onwards until disease progression: 16 mg/kg every 4 wk, 1st dose to be given at wk 25.

History of severe hypersensitivity (eg, anaphylactic reactions).

Permanently discontinue therapy if anaphylactic or life-threatening (Grade 4) reactions occur. Interrupt infusion for reactions of any severity; if ocular symptoms occur. Consider withholding therapy until recovery of neutrophils & platelets. Suspend treatment in patients who develop HBV reactivation. Monitor patients w/ neutropenia for signs of infection; clinical & lab signs of HBV reactivation during & for at least 6 mth following end of treatment. Severe &/or serious infusion-related reactions including anaphylactic reactions; bronchospasm, hypoxia, dyspnea, HTN, tachycardia, headache, laryngeal & pulmonary edema, & ocular adverse reactions including choroidal effusion, acute myopia & acute angle closure glaucoma. May increase neutropenia or thrombocytopenia induced by background therapy. Premed w/ antihistamines, antipyretics & corticosteroids, & frequently monitor patients during entire infusion. Consider post-infusion medications including short- & long-acting bronchodilators & inhaled corticosteroids in patients w/ history of COPD. Type & screen patients prior to starting therapy. Perform HBV screening before treatment initiation. Periodically monitor CBC during treatment. +ve result in indirect Coombs test. Interference w/ determination of complete response & disease progression in patients w/ IgG kappa myeloma protein. May affect ability to drive & use machines due to fatigue. Women of reproductive potential should use effective contraception during treatment & for 3 mth after last dose. Contraindicated in pregnancy & not to breastfeed in combination w/ lenalidomide, pomalidomide or thalidomide. Potential risk to fetus. Defer administering live vaccines to neonates & infants exposed in utero until hematology evaluation is completed. Ped patients.

URTI, neutropenia, infusion-related reactions, thrombocytopenia, diarrhea, constipation, anemia, peripheral sensory neuropathy, fatigue, peripheral edema, nausea, cough, pyrexia, dyspnea, & asthenia. Pneumonia.

Interference w/ indirect Coombs test. False +ve serum protein electrophoresis & immunofixation assay results.

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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