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Clinical Trial
. 2023 Aug;10(8):e624-e632.
doi: 10.1016/S2352-3026(23)00157-6.

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

Paul G Rubinstein  1 , Page C Moore  2 , Milan Bimali  2 , Jeanette Y Lee  2 , Michelle A Rudek  3 , Amy Chadburn  4 , Lee Ratner  5 , David H Henry  6 , Ethel Cesarman  4 , Camille E DeMarco  7 , Dominique Costagliola  8 , Yassine Taoufik  9 , Juan Carlos Ramos  10 , Elad Sharon  11 , Erin G Reid  12 , Richard F Ambinder  3 , Ronald Mitsuyasu  13 , Nicolas Mounier  14 , Caroline Besson  15 , Ariela Noy  16 ; AIDS Malignancy Consortium; Lymphoma Study Association
Collaborators, Affiliations
Clinical Trial

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

Paul G Rubinstein et al. Lancet Haematol. 2023 Aug.

Abstract

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 ClinicalTrials.gov, 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.

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Conflict of interest statement

Declaration of interests AN has an MSK core grant National Institutes of Health (NIH) P30 CA008748 and NIH grant PO1 1568 G TA390. MAR is supported by the Johns Hopkins University Core Grant P30CA006973, contracts with Cullinan Apollo and RenovoRx, and is a founder and serves on the Board of Directors of Geminus Therapeutics. EGR is the co-chair of the National Comprehensive Cancer Network panel of Cancer in Persons With HIV and Kaposi Sarcoma, an unpaid position. PCM is supported by an MSK core grant (P30CA008748). PGR, AN, EGR, PCM, MB, JYL, RM, DHH, JCR, RFA, CD, MAR, AC, LR, and EC are supported in part by National Cancer Institute-sponsored AIDS Malignancy Consortium grant UM1CA121947 and UM1CA181255. RFA is supported by John Hopkins Cancer Center (5P30CA006973). CB and NM are supported in part by Lymphoma Study Association, and DC and YT are supported in part by the French Agency for Research on AIDS and Viral Hepatitis. DC also has contracts with Jansen and speaker bureau funding from Gilead and Pfizer. All other authors declare no competing interests.

Figures

Figure 1.
Figure 1.. Trial Profile.
Figure 2.
Figure 2.. Progression Free (PFS) and Overall Survival (OS) Analysis.
(A) Kaplan-Meier curves showing PFS and OS for the entire cohort and (B) for patients with stage III/IV HIV-associated cHL.
Figure 3.
Figure 3.. Absolute number of CD4/8+ T-cells, and trends of patients with detectable HIV viral Loads at baseline, during therapy, and post-therapy evaluation.
Box plots assessing the pattern of (A) the absolute CD4+ T-cell counts (cells/μL), (B) CD8+ T-cell counts (cells/μL), and (C) detectable viral loads of the HIV-associated cHL patients enrolled in AMC085.
See this image and copyright information in PMC

Comment in

References

    1. Olszewski, Adam J; Castillo, Jorge J. Outcomes of HIV-associated Hodgkin lymphoma in the era of antiretroviral therapy. AIDS. 2016;30:787–796. - PubMed
    1. Shiels MS, Pfeiffer RM, Gail MH, Hall HI, Li J, Chaturvedi AK, et al. Cancer burden in the HIV- infected population in the United States. Journal of the National Cancer Institute. 2011; 103:753–762. - PMC - PubMed
    1. Besson C, Lancar R, Prevot S, Brice P, Meyohas MC, Marchou B, et al. High Risk Features Contrast With Favorable Outcomes in HIV-associated Hodgkin Lymphoma in the Modern cART Era, ANRS CO16 LYMPHOVIR Cohort. Clin Infect Dis. 2015. Nov 1; 61(9):1469–75. DOI: 10.1093/cid/civ627 - DOI - PubMed
    1. Rubinstein PG, Aboulafia DM, Zloza A. Malignancies in HIV/AIDS: from epidemiology to therapeutic challenges. Aids. 2014; 28(4):453–465. - PMC - PubMed
    1. Levine AM, Li P, et al. Chemotherapy consisting of doxorubicin, bleomycin, vinblastine, and dacarbazine with granulocyte-colony-stimulating factor in HIV-infected patients with newly diagnosed Hodgkin’s disease: a prospective, multi-institutional AIDS clinical trials group study (ACTG 149). J Acquir Immune Defic Syndr. 2000; 24(5): 444–50. - PubMed

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