Adcetris

Classical Hodgkin lymphoma (cHL) — previously untreated Stage III or IV (with doxorubicin, vinblastine, and dacarbazine); post-ASCT consolidation in patients at high risk of relapse or progression; after failure of ASCT or ≥2 prior multi-agent chemotherapy regimens; Systemic anaplastic large cell lymphoma (sALCL) — previously untreated (with CHP), or after failure of at least one prior multi-agent chemotherapy regimen; Primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides — who have received prior systemic therapy

Standard dose: 1.8 mg/kg IV over 30 minutes every 3 weeks (maximum 180 mg)
Previously untreated cHL (with AVD): 1.2 mg/kg (max 120 mg) Days 1 and 15 of 28-day cycle for up to 12 cycles
Post-ASCT consolidation: 1.8 mg/kg q3w starting 4-6 weeks post-ASCT, up to 16 cycles
pcALCL/MF: 1.8 mg/kg q3w up to 16 cycles

For injection: 50 mg lyophilized powder in single-dose vial

Concomitant use with bleomycin due to pulmonary toxicity.

• Peripheral Neuropathy: Reported in 67% of patients (motor 7%, sensory 64%). Monitor and dose-modify.
• Anaphylaxis and Infusion Reactions: Premedicate for patients with prior infusion reaction.
• Hematologic Toxicities: Fatal and serious febrile neutropenia reported. Grade 3-4 neutropenia in 54-58%. Dose delay and G-CSF prophylaxis recommended.
• Serious Infections and Opportunistic Infections: Including pneumonia, sepsis, CMV, herpes zoster. Consider antimicrobial prophylaxis.
• Tumor Lysis Syndrome: Monitor and manage.
• Hepatotoxicity: Including fatal outcomes. Monitor LFTs and bilirubin.
• PML: Monitor for signs/symptoms. Withhold at first sign and evaluate.
• Pulmonary Toxicity: Including pneumonitis and ARDS. Do not administer with bleomycin.
• Stevens-Johnson Syndrome/TEN: Discontinue and treat.
• GI Complications: Including fatal perforation, hemorrhage, erosion, ulcer, intestinal obstruction, enterocolitis, and ileus.

Peripheral neuropathy (67%), fatigue (49%), nausea (42%), diarrhea (36%), neutropenia (39%), upper respiratory tract infection (25%), pyrexia (24%), constipation (16%), vomiting (17%), alopecia (13%)

Consult the complete prescribing information for a comprehensive list of adverse reactions and their frequencies.

Consult the complete prescribing information for drug interactions, including effects on CYP enzymes, transporters, and concomitant medications that may require dose adjustments or monitoring.

Consult the full prescribing information for pregnancy-related considerations.

Refer to prescribing information for lactation guidance.

Pediatric safety and efficacy information is detailed in the full label.

Dose modifications for organ impairment are specified in the complete prescribing information.

Brentuximab vedotin is an antibody-drug conjugate consisting of a chimeric anti-CD30 IgG1 antibody conjugated to monomethyl auristatin E (MMAE), a microtubule-disrupting agent, via a protease-cleavable linker. It binds CD30 on the cell surface and is internalized, releasing MMAE which binds to tubulin and disrupts the microtubule network, inducing cell cycle arrest and apoptotic death of CD30-expressing tumor cells.

ADC half-life: approximately 4-6 days. MMAE (payload) half-life: 3-4 days. Tmax (ADC): end of infusion. Vd: approximately 6-10 L. Clearance: 1.46 L/day. Steady-state by approximately Cycle 3. MMAE is metabolized by CYP3A4. Primarily excreted in feces (72%) and urine (28%).

Clinical efficacy and safety data supporting the approval are available in the full prescribing information and from the clinical trials listed below.

• SG035-0003 — Brentuximab vedotin in relapsed/refractory Hodgkin lymphoma after auto-SCT. Phase II, n=102.
  🔬 NCT00848926 ↗ 📄 Primary Publication ↗
• ECHELON-1 — Brentuximab vedotin + AVD vs. ABVD in 1L advanced Hodgkin lymphoma. Phase III, n=1334.
  🔬 NCT01712490 ↗ 📄 Primary Publication ↗

Adcetris has FDA-approved indications across the following cancer types covered on PipelineEvidence: