Brentuximab vedotin with AVD for stage II-IV HIV-related Hodgkin lymphoma (AMC 085): phase 2 results from an open-label, single arm, multicentre phase 1/2 trial.

TitleBrentuximab vedotin with AVD for stage II-IV HIV-related Hodgkin lymphoma (AMC 085): phase 2 results from an open-label, single arm, multicentre phase 1/2 trial.
Publication TypeJournal Article
Year of Publication2023
AuthorsRubinstein PG, Moore PC, Bimali M, Lee JY, Rudek MA, Chadburn A, Ratner L, Henry DH, Cesarman E, DeMarco CE, Costagliola D, Taoufik Y, Ramos JCarlos, Sharon E, Reid EG, Ambinder RF, Mitsuyasu R, Mounier N, Besson C, Noy A
Corporate AuthorsAIDS Malignancy Consortium, Lymphoma Study Association
JournalLancet Haematol
Date Published2023 Aug
KeywordsAntineoplastic Combined Chemotherapy Protocols, Brentuximab Vedotin, Doxorubicin, HIV Infections, Hodgkin Disease, Humans

BACKGROUND: Brentuximab vedotin in combination with doxorubicin, vinblastine, and dacarbazine (AVD) is approved in the upfront setting for advanced stage classical Hodgkin lymphoma (cHL). People living with HIV have been excluded from these studies. We aimed to understand the activity and safety of brentuximab vedotin-AVD in people living with HIV diagnosed with Hodgkin lymphoma, while focusing on HIV disease parameters and antiretroviral therapy (ART) interactions.

METHODS: We present the phase 2 portion of a multicentre phase 1/2 study. Eligible patients were 18 years or older, had untreated stage II-IV HIV-associated cHL (HIV-cHL), a Karnofsky performance status of more than 30%, a CD4+ T-cell count of 50 cells per μL or more, were required to take ART, and were not on strong CYP3A4 or P-glycoprotein inhibitors. Patients were treated intravenously with 1·2 mg/kg of brentuximab vedotin (recommended phase 2 dose) with standard doses of AVD for six cycles on days 1 and 15 of a 28-day cycle. The primary endpoint of the phase 2 portion was 2-year progression-free survival (PFS), assessed in all eligible participants who began treatment. Accrual has been completed. This trial is registered at, NCT01771107.

FINDINGS: Between March 8, 2013, and March 7, 2019, 41 patients received study therapy with a median follow up of 29 months (IQR 16-38). 34 (83%) of 41 patients presented with stage III-IV and seven (17%) with stage II unfavourable HIV-cHL. 37 (90%) of 41 patients completed therapy, all 37 of whom achieved complete response. The 2-year PFS was 87% (95% CI 71-94) and the overall survival was 92% (78-97). The most common grade 3 or worse adverse events were peripheral sensory neuropathy (four [10%] of 41 patients), neutropenia (18 [44%]), and febrile neutropenia (five [12%]). One treatment-related death was reported, due to infection.

INTERPRETATION: Brentuximab vedotin-AVD was highly active and had a tolerable adverse event rate in HIV-cHL and is an important therapeutic option for people with HIV-cHL. The complete reponse rate is encouraging and is possibly related to a unique aspect of HIV-cHL biology. Upcoming 5-year data will evaluate the sustainability of the outcomes obtained.

FUNDING: National Institutes of Health and National Cancer Institute.

Alternate JournalLancet Haematol
PubMed ID37532416
PubMed Central IDPMC10859222
Grant ListP30 CA006973 / CA / NCI NIH HHS / United States
P30 CA008748 / CA / NCI NIH HHS / United States
UM1 CA121947 / CA / NCI NIH HHS / United States
UM1 CA181255 / CA / NCI NIH HHS / United States
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