Overview
11 DESCRIPTION ADCETRIS (brentuximab vedotin) is a CD30-directed antibody and microtubule inhibitor conjugate consisting of three components: 1) the chimeric IgG1 antibody cAC10, specific for human CD30, 2) the microtubule disrupting agent MMAE, and 3) a protease-cleavable linker that covalently attaches MMAE to cAC10. Brentuximab vedotin has an approximate molecular weight of 153 kDa.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action CD30 is a member of the tumor necrosis factor receptor family and is expressed on the surface of sALCL cells and on Hodgkin Reed-Sternberg (HRS) cells in cHL. CD30 is variably expressed in other T-cell lymphomas. Expression of CD30 on healthy tissue and cells is limited. In vitro data suggest that signaling through CD30-CD30L binding may affect cell survival and proliferation. Brentuximab vedotin is an antibody-drug conjugate (ADC). The antibody is a chimeric IgG1 directed against CD30. The small molecule, MMAE, is a microtubule-disrupting agent. MMAE is covalently attached to the antibody via a linker.
Indications
- 1 INDICATIONS AND USAGE ADCETRIS is a CD30-directed antibody and microtubule inhibitor conjugate indicated for treatment of: • Adult patients with previously untreated Stage III or IV classical Hodgkin lymphoma (cHL), in combination with doxorubicin, vinblastine, and dacarbazine ( 1.1 ). • Pediatric patients 2 years and older with previously untreated high risk classical Hodgkin lymphoma (cHL), in combination with doxorubicin, vincristine, etoposide, prednisone, and cyclophosphamide ( 1.2 ).
Common Doses
- 1.8 mg
- 180 mg
- 1.2 mg
- 120 mg
Dosage
2 DOSAGE AND ADMINISTRATION • Administer only as an intravenous infusion over 30 minutes ( 2.1 ). • The recommended dosage as monotherapy for adult patients is 1.8 mg/kg up to a maximum of 180 mg every 3 weeks ( 2.1 ). • The recommended dosage in combination with chemotherapy for adult patients with previously untreated Stage III or IV cHL is 1.2 mg/kg up to a maximum of 120 mg every 2 weeks for a maximum of 12 doses ( 2.1 ). • The recommended dosage in combination with chemotherapy for pediatric patients 2 years and older with previously untreated high risk cHL is 1.
Black Box Warning
WARNING: PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML) JC virus infection resulting in PML and death can occur in patients receiving ADCETRIS [see Warnings and Precautions (5.9) , Adverse Reactions (6.1) ] . WARNING: PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML) See full prescribing information for complete boxed warning. JC virus infection resulting in PML and death can occur in patients receiving ADCETRIS ( 5.9 , 6.1 ).
Contraindications
- 4 CONTRAINDICATIONS ADCETRIS is contraindicated with concomitant bleomycin due to pulmonary toxicity (e.g., interstitial infiltration and/or inflammation) [see Adverse Reactions (6.1) ] . Concomitant use with bleomycin due to pulmonary toxicity (4) .
Side Effects
- 6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: • Peripheral Neuropathy [see Warnings and Precautions (5.1) ] • Anaphylaxis and Infusion Reactions [see Warnings and Precautions (5.2) ] • Hematologic Toxicities [see Warnings and Precautions (5.3) ] • Serious Infections and Opportunistic Infections [see Warnings and Precautions (5.4) ] • Tumor Lysis Syndrome [see Warnings and Precautions (5.5) ] o Increased Toxicity in the Presence of Severe Renal Impairment [see Warnings and Precautions (5.
Interactions
- 7 DRUG INTERACTIONS Concomitant use of strong CYP3A4 inhibitors or inducers has the potential to affect the exposure to monomethyl auristatin E (MMAE) ( 7.1 ). 7.1 Effect of Other Drugs on ADCETRIS CYP3A4 Inhibitors: Co-administration of ADCETRIS with ketoconazole, a potent CYP3A4 inhibitor, increased exposure to MMAE [see Clinical Pharmacology (12.3) ], which may increase the risk of adverse reaction. Closely monitor adverse reactions when ADCETRIS is given concomitantly with strong CYP3A4 inhibitors.