Initial US Approval:
2011
Key Clinical Studies:
ECHELON-3 (NCT04404283)
Drug Class/Description:
CD30-directed antibody and microtubule inhibitor conjugate
Indications and Usage:
- Adult patients with previously untreated stage III or IV classical Hodgkin lymphoma (cHL), in combination with doxorubicin, vinblastine, and dacarbazine.
- Pediatric patients 2 years and older with previously untreated high risk cHL, in combination with doxorubicin, vincristine, etoposide, prednisone, and cyclophosphamide.
- Adult patients with cHL at high risk of relapse or progression as post-autologous hematopoietic stem cell transplantation (auto-HSCT) consolidation.
- Adult patients with cHL after failure of auto-HSCT or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not auto-HSCT candidates.
- Adult patients with previously untreated systemic anaplastic large cell lymphoma (sALCL) or other CD30-expressing peripheral T-cell lymphomas (PTCL), including angioimmunoblastic T-cell lymphoma and PTCL not otherwise specified (NOS), in combination with cyclophosphamide, doxorubicin, and prednisone.
- Adult patients with sALCL after failure of at least one prior multi-agent chemotherapy regimen.
- Adult patients with primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides (MF) who have received prior systemic therapy.
- Adult patients with relapsed or refractory large B-cell lymphoma (LBCL), including diffuse large B-cell lymphoma (DLBCL) NOS, DLBCL arising from indolent lymphoma, or high-grade B-cell lymphoma (HGBL), after two or more lines of systemic therapy who are not eligible for auto-HSCT or CAR T-cell therapy, in combination with lenalidomide and a rituximab product.
Dosage Administration:
- Administer only as an intravenous infusion over 30 minutes.
- The recommended dosage as monotherapy for adult patients is 1.8 mg/kg up to a maximum of 180 mg every 3 weeks.
- 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.
- The recommended dosage in combination with chemotherapy for pediatric patients 2 years and older with previously untreated high risk cHL is 1.8 mg/kg up to a maximum of 180 mg every 3 weeks for a maximum of 5 doses.
- The recommended dosage in combination with chemotherapy for adult patients with previously untreated PTCL is 1.8 mg/kg up to a maximum of 180 mg every 3 weeks for 6 to 8 doses.
- The recommended dosage in combination with lenalidomide and a rituximab product for adult patients with relapsed or refractory LBCL is 1.2 mg/kg up to a maximum of 120 mg every 3 weeks.
- Avoid use in patients with severe renal impairment.
- Reduce dose in patients with mild hepatic impairment; avoid use in patients with moderate or severe hepatic impairment.
Dosage Forms and Strengths:
For injection: 50 mg lyophilized powder in a single-dose vial.
Contraindications:
Concomitant use with bleomycin due to pulmonary toxicity.
Warnings and Precautions:
- Peripheral Neuropathy: Monitor patients for neuropathy and institute dose modifications accordingly.
- Anaphylaxis and Infusion Reactions: If an infusion reaction occurs, interrupt the infusion. If anaphylaxis occurs, immediately discontinue the infusion.
- Hematologic Toxicities: Monitor complete blood counts. Monitor for signs of infection. Manage using dose delays and growth factor support.
- Serious Infections and Opportunistic Infections: Closely monitor patients for the emergence of bacterial, fungal or viral infections.
- Tumor Lysis Syndrome: Closely monitor patients with rapidly proliferating tumor or high tumor burden.
- Hepatotoxicity: Monitor liver enzymes and bilirubin.
- Pulmonary Toxicity: Monitor patients for new or worsening symptoms.
- Serious Dermatologic Reactions: Discontinue if Stevens-Johnson syndrome or toxic epidermal necrolysis occurs.
- Gastrointestinal Complications: Monitor patients for new or worsening symptoms.
- Hyperglycemia: Monitor patients for new or worsening hyperglycemia. Manage with anti-hyperglycemic medications as clinically indicated.
- Embryo-Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential and males with female partners of reproductive potential of the potential risk to a fetus and to use effective contraception.
Adverse Reactions:
The most common adverse reactions (≥ 20%) are peripheral neuropathy, nausea, fatigue, musculoskeletal pain, constipation, diarrhea, vomiting, pyrexia, upper respiratory tract infection, mucositis, abdominal pain, and rash.
The most common laboratory abnormalities (≥ 20%) are decreased neutrophils, increased creatinine, decreased hemoglobin, decreased lymphocytes, increased glucose, increased alanine aminotransferase (ALT), and increased aspartate aminotransferase (AST).
Drug Interactions:
- Concomitant use of strong CYP3A4 inhibitors or inducers has the potential to affect the exposure to monomethyl auristatin E (MMAE).
Use in Specific Populations:
- Moderate or Severe Hepatic Impairment or Severe Renal Impairment: MMAE exposure and adverse reactions are increased.
- Lactation: Advise women not to breastfeed.
Adapted from:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/125388Orig1s108lbl.pdf
Every health-care provider should make their own determination regarding specific safe and appropriate patient care practices, including drug dosages and indications. The provider should always consult the most recent prescribing/product information. FDA Focus information is not guaranteed to be accurate, complete, or current. JADPRO and its editors, authors, reviewers, and commentators cannot be held responsible for any liability incurred as a consequence of the application of any of the information listed within.
