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AIDS. 2018 Mar 13;32(5):605-611. doi: 10.1097/QAD.0000000000001729.

Brentuximab vedotin with AVD shows safety, in the absence of strong CYP3A4 inhibitors, in newly diagnosed HIV-associated Hodgkin lymphoma.

Author information

1
John H. Stroger Jr. Hospital of Cook County (Cook County Hospital).
2
The Ruth M. Rothstein CORE Center, Rush University Medical Center, Chicago, Illinois.
3
University of Arkansas for Medical Sciences, Little Rock, Arkansas.
4
Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland.
5
Abramson Cancer Center, Pennsylvania Hospital, Philadelphia, Pennsylvania.
6
Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, Florida.
7
Washington University School of Medicine, St. Louis, Missouri.
8
San Diego Moores Cancer Center, University of California, La Jolla, California.
9
Cancer Therapy Evaluation Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, Maryland.
10
Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College, New York, New York, USA.

Abstract

OBJECTIVE:

Brentuximab vedotin is a Food and Drug Administration approved anti-CD30 antibody drug conjugate potently active in Hodgkin lymphoma. Trials of brentuximab vedotin with doxorubicin, vinblastine, and dacarbazine (AVD-BV) excluded patients with HIV. We studied the safety of AVD-BV in newly diagnosed HIV-associated classical Hodgkin lymphoma .

DESIGN AND METHODS:

Patients diagnosed with stage II-IV HIV-associated classical Hodgkin lymphoma received AVD-BV on days 1 and 15 every 28 days for six cycles. Anti-HIV medications with strong CYP3A4 inhibition were excluded. This phase 1 trial followed a 3+3 dose de-escalation design started with brentuximab vedotin at 1.2 mg/kg with standard dosing of AVD. Dose-limiting toxicities were defined in cycle one.

RESULTS:

Seven patients were enrolled with six being evaluable: five of six stage III/IV, three with an international prognostic score at least 4. With no dose-limiting toxicities identified, all six were treated at the 1.2 mg/kg dose. Only five grade (G) three nonhematological adverse events were noted in three patients: pulmonary infection, diarrhea, and peripheral neuropathy. No G4/5 adverse events occurred. PET/computer tomography was negative in five of six after cycle 2 and six of six post therapy. Progression-free survival was 100% at 25 months with all patients in remission. One patient was deemed ineligible for taking ritonavir, a strong CYP3A4 inhibitor, but developed G3/4 adverse events including febrile neutropenia, and pancreatitis and though consented was excluded from all evaluation.

CONCLUSION:

AVD-BV was well tolerated at recommended phase 2 dose of 1.2 mg/kg. Concurrent strong CYP3A4 inhibitors should be avoided. A phase 2 study of AVD-BV is currently enrolling (NCT01771107).

PMID:
29280762
PMCID:
PMC5832596
[Available on 2019-03-13]
DOI:
10.1097/QAD.0000000000001729

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