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.
Journal
The Lancet. Haematology
ISSN: 2352-3026
Titre abrégé: Lancet Haematol
Pays: England
ID NLM: 101643584
Informations de publication
Date de publication:
Aug 2023
Aug 2023
Historique:
received:
24
01
2023
revised:
08
05
2023
accepted:
16
05
2023
medline:
4
8
2023
pubmed:
3
8
2023
entrez:
2
8
2023
Statut:
ppublish
Résumé
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. 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 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. 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. National Institutes of Health and National Cancer Institute.
Sections du résumé
BACKGROUND
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
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
FINDINGS
RESULTS
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
CONCLUSIONS
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
BACKGROUND
National Institutes of Health and National Cancer Institute.
Identifiants
pubmed: 37532416
pii: S2352-3026(23)00157-6
doi: 10.1016/S2352-3026(23)00157-6
pii:
doi:
Substances chimiques
Brentuximab Vedotin
7XL5ISS668
Doxorubicin
80168379AG
Banques de données
ClinicalTrials.gov
['NCT01771107']
Types de publication
Clinical Trial, Phase II
Clinical Trial, Phase I
Multicenter Study
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e624-e632Investigateurs
Stefan K Barta
(SK)
Ayad Hamdan
(A)
François Boué
(F)
Pierre Delobel
(P)
Lionel Galicier
(L)
Paul Coppo
(P)
Hervé Ghesquières
(H)
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2023 Elsevier Ltd. All rights reserved.
Déclaration de conflit d'intérêts
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.