Feasibility of Cellular Therapies in HIV Infected Patients: A Monocentric Retrospective Analysis

Background: Highly active antiretroviral therapy (HAART) radically changed the prognosis of patients living with HIV/AIDS (PLWHA). However, the risk of developing cancer remains higher than in the general population, especially for AIDS-classifying cancers such as aggressive lymphomas. Despite the progress made in the last decades, HIV infection still represents an obstacle to receive intensive oncological care such as allogeneic stem cell transplantation (allo-SCT) and remains an exclusion criterion in most clinical trials restraining access to innovative therapy for PLWHA.

Aim:

In order to demonstrate the feasibility of allo-SCT or chimeric antigen receptor T cells (CAR-T) therapy in PLWHA, and to report clinical, biological, and immunological and virological characteristics of PLWHA treated with these cellular therapies, we report the largest French cohort of HIV positive patients treated with allo-SCT or CAR-T cells.

Methods: Retrospective observational study of all PLWHA treated by allo-SCT or CAR-T cell at Institut Paoli-Calmettes (Marseille, France) between October 2019 and June 2022.

Results:

Five patients (pts) received an allo-SCT between 2019 and 2021; median age was 52 years (42-70). Four patients had an HIV infection diagnosed since more than 10 years whereas 3 were treated by antiretroviral therapy (ART) and had an undetectable viral load (UVL). One patient (pt) presented with synchronous diagnosis of hematological malignancy and HIV infection. At the time of allo-SCT, all pts were treated by ART and had UVL before the transplant. Three pts had lymphoid malignancies (1 diffuse large B cell lymphoma relapse after Car T), 2 had myeloid malignancies. All pts had an HCT-CI score ≥ 3 and 3 donors had a homozygous CCR5-Delta32 mutation known to be protective against HIV infection. Four pts received a non-myeloablative conditioning regimen, and 1 pt received a reduced intensity conditioning regimen. Four pts had a mismatched unrelated donor, 1 pt had a matched unrelated donor. One pt had acute graft failure and died of relapse 5 months after transplant. Grade 2-4 acute graft versus host disease (aGVHD) occurred in 3 pts, none of them developed moderate to severe chronic GVHD. No treatment related mortality was observed. One pt had viral (CMV and EBV) reactivation without disease. After a median follow up of 19.5 months (6-23), four pts are still in complete remission (CR) and remain on ART with UVL.

Four pts received CAR-T cells for relapsed or refractory diffuse large B cell lymphoma (DLBCL) between 2019 and 2022; median age was 53 years (44-61). Two pts had an HIV infection diagnosed since more than 10 years before the diagnosis of the hematological malignancy and 1 was treated by ART with UVL. One pt presented with synchronous diagnosis of hematological malignancy and HIV infection. Median prior lines of treatment before CAR-T cells was 2.5. At the time of leukapheresis: viral load was undetectable for 3 pts and was around 100 copies/ml for the remaining patient. CAR-T cells were successfully produced in all cases. All pts were treated with axicabtagene-ciloleucel (the only CAR T available for PLWHA in France). Grade 1 2 cytokine release syndrome occurred in all patients. One patient had grade 2 neurotoxicity. No documented severe infection was recorded. After a median follow up of 10 months (2-35), best response was: CR for 2 pts, partial response (PR) and stable disease (SD) for 1 pt respectively. One pt died of progressive disease 8 months after CAR-T cell infusion, 1 pt progressed and underwent allo-SCT, 1 pt is still in CR and 1 pt obtained PR 1 month after infusion. All patients remain on ART without virologic failure.

Conclusion: We report the largest French series of CAR-T and allo-SCT in PLWHA. With a median follow-up of 10 months, 6 of 8 patients are still alive: 5 in CR and 1 in PR. Importantly, no treatment related deaths were observed. Furthermore, in this highly treated and severely immunocompromised pts, no symptomatic viral recrudescence occurred. ART discontinuation is programmed for 2 pts transplanted with CCR5-Delta32 mutated donors.

Allo-SCT and CAR-T cell therapy are feasible and effective in PLWHA. HIV infection must be considered to evaluate the feasibility of these procedures but is not limiting by itself, especially in patients demonstrating virological success. Importantly, allo-SCT remains to date the only curative procedure for HIV infection.

Inchiappa:abbvie: Honoraria; Janssen: Honoraria; Gilead: Honoraria; Astra Zeneca: Honoraria. Brisou:Gilead: Honoraria; BMS: Honoraria; Novartis: Honoraria; Incyte: Honoraria. Laroche:Gilead: Honoraria. Faucher:Gilead: Honoraria; MSD: Honoraria; ViiV: Honoraria. Bregigeon:Gilead: Honoraria; Janssen: Honoraria; MSD: Honoraria; ViiV: Honoraria. Chabannon:GILEAD: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; NOVARTIS: Speakers Bureau; BMS/CELGENE: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; JANSSEN PHARMACEUTICALS: Membership on an entity's Board of Directors or advisory committees; TERUMO BCT: Speakers Bureau; MILTENYI BIOTECH: Research Funding; FRESENIUS KABI: Research Funding; EBMT: Membership on an entity's Board of Directors or advisory committees; BELLICUM PHARMACEUTICALS: Membership on an entity's Board of Directors or advisory committees; SANOFI SA: Honoraria, Research Funding, Speakers Bureau. Vey:Amgen: Honoraria; BMS: Honoraria; Jazz Pharmaceuticals: Honoraria; Janssen: Honoraria; Novartis: Honoraria, Research Funding; Roche: Honoraria.