Seattle Genetics, Inc's Adcetris

The FDA has granted acceleration approval for Adcetris (brentuximba vedotin) for the treatment of Hodgkin lymphoma.

The FDA has granted accelerated approval to Seattle Genetics, Inc’s Adcetris (brentuximab vedotin). Adcetris is indicated for the treatment of Hodgkin lymphoma (HL) after failure of autologous stem cell transplant (ASCT) or after failure of at least 2 prior multiagent chemotherapy regimens in patients who are not candidates for ASCT. It is also approved for the treatment of systemic anaplastic large cell lymphoma (ALCL) after failure of at least 1 prior multiagent chemotherapy regimen. Both indications are based on response rates; no data are available to demonstrate that patients using Adcetris experienced an improvement in outcomes or survival.¹

Adcetris is the first new FDAapproved agent for HL in more than 30 years and the first agent ever specifically approved for ALCL.²

Pharmacology and Pharmacokinetics

Adcetris is a CD30-directed antibodydrug conjugate (ADC). When the ADC binds to the CD30-expressing cells, the ADC-CD30 complex is internalized, and monomethyl auristatin E (MMAE) is released via proteolytic cleavage. When MMAE binds to tubulin, the microtubule network within the cell is disrupted, leading to cell cycle arrest and cellular apoptosis.^1,3

Age, gender, and race do not appear to affect the pharmacokinetics of Adcetris. The influence of renal and/ or hepatic impairment on the pharmacokinetics of Adcetris has not yet been determined.¹

Dosage and Administration

Adcetris should be given as a 1.8 mg/ kg intravenous infusion over 30 minutes every 3 weeks. Adcetris should not be administered as an intravenous bolus or push. Treatment should be continued until a maximum of 16 cycles are completed, disease progression occurs, or unacceptable toxicity occurs.

Dose modification is required if the following occur:

• Peripheral neuropathy, new or worsening Grade 2 or 3: hold until neuropathy improves to Grade 1 or baseline, then restart at 1.2 mg/kg.
• Peripheral neuropathy, Grade 4: discontinue Adcetris.
• Neutropenia, Grade 3 or 4: hold until neutropenia resolves to baseline or Grade 2 or lower. Consider growth factor support for subsequent cycles.
• Neutropenia, recurrent Grade 4 despite growth factors: consider discontinuation or dose reduction to 1.2 mg/kg.¹

Clinical Trials

Adcetris was studied in a single-arm trial of 102 patients with HL who had relapsed after ASCT. Seventy-three percent of patients achieved the primary end point of complete or partial cancer shrinkage or disappearance, 32% of whom experienced complete remission and 40% of whom experienced partial remission. The average duration of response was 6.7 months.

The single-arm trial that evaluated the role of Adcetris for the treatment of ALCL consisted of 58 patients in whom the disease had relapsed. The primary end point of complete or partial cancer shrinkage or disappearance was achieved by 86% of patients, 57% of whom experienced complete remission and 29% of whom experienced partial remission. The average duration of response was 12.6 months.^2,3

Contraindications, Warnings, and Precautions

There are no contraindications to treatment with Adcetris. Patients should be monitored for peripheral neuropathy and the dose of Adcetris should be adjusted appropriately if peripheral neuropathy occurs. If an infusion reaction occurs, the infusion should be interrupted and the reaction should be managed with appropriate medical intervention. If a patient experiences anaphylaxis during the infusion, the infusion should be stopped immediately and medical management initiated.

Complete blood counts should be monitored prior to each dose of Adcetris. Patients in whom the tumor is rapidly proliferating and who have a high tumor burden are at risk for tumor lysis syndrome and should be monitored accordingly. Adcetris should be discontinued immediately if Stevens-Johnson syndrome occurs.

Adcetris is Pregnancy Category D. Women who are pregnant should be aware of the potential for fetal harm during treatment with Adcetris. Adcetris is not approved for use in pediatric patients. Close monitoring is required for patients receiving strong CYP3A4 inhibitors during treatment with Adcetris. SPT

Monica Holmberg, PharmD, BCPS, is a clinical pharmacist who resides in Phoenix, Arizona.

References

1. Adcetris complete prescribing information. www.adcetris.com/_pdf/Adcetris_USPI_2011.pdf. Accessed September 2011.

2. FDA approves Adcetris to treat two types of lymphoma. www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm268781.htm. Accessed September 2011.

3. Seattle Genetics announces FDA accelerated approval of ADCETRIS™

(brentuximab vedotin) for two indications. www.adcetris.com/_pdf/FDA_Approval_FINAL_19Aug11.pdf. Accessed September 2011.