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

Paul G. Rubinstein, Page C. Moore, Michelle Rudek-Renaut, David H. Henry, Juan C. Ramos, Lee Ratner, Erin Reid, Elad Sharon, Ariela Noy

Research output: Contribution to journalArticle

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).

Original languageEnglish (US)
Pages (from-to)605-611
Number of pages7
JournalAIDS
Volume32
Issue number5
DOIs
StatePublished - Mar 13 2018

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Hodgkin Disease
HIV
Safety
Cytochrome P-450 CYP3A
Ritonavir
Febrile Neutropenia
Dacarbazine
Vinblastine
Peripheral Nervous System Diseases
United States Food and Drug Administration
Pancreatitis
Doxorubicin
Disease-Free Survival
cAC10-vcMMAE
Cytochrome P-450 CYP3A Inhibitors
Anti-Idiotypic Antibodies
Diarrhea
Tomography
Lung
Infection

Keywords

  • antibody drug conjugate
  • HIV-associated Hodgkin lymphoma
  • targeted therapy

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

Brentuximab vedotin with AVD shows safety, in the absence of strong CYP3A4 inhibitors, in newly diagnosed HIV-associated Hodgkin lymphoma. / Rubinstein, Paul G.; Moore, Page C.; Rudek-Renaut, Michelle; Henry, David H.; Ramos, Juan C.; Ratner, Lee; Reid, Erin; Sharon, Elad; Noy, Ariela.

In: AIDS, Vol. 32, No. 5, 13.03.2018, p. 605-611.

Research output: Contribution to journalArticle

Rubinstein, Paul G. ; Moore, Page C. ; Rudek-Renaut, Michelle ; Henry, David H. ; Ramos, Juan C. ; Ratner, Lee ; Reid, Erin ; Sharon, Elad ; Noy, Ariela. / Brentuximab vedotin with AVD shows safety, in the absence of strong CYP3A4 inhibitors, in newly diagnosed HIV-associated Hodgkin lymphoma. In: AIDS. 2018 ; Vol. 32, No. 5. pp. 605-611.
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T1 - Brentuximab vedotin with AVD shows safety, in the absence of strong CYP3A4 inhibitors, in newly diagnosed HIV-associated Hodgkin lymphoma

AU - Rubinstein, Paul G.

AU - Moore, Page C.

AU - Rudek-Renaut, Michelle

AU - Henry, David H.

AU - Ramos, Juan C.

AU - Ratner, Lee

AU - Reid, Erin

AU - Sharon, Elad

AU - Noy, Ariela

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AB - 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).

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