Real-World Outcomes of Aggressive B-Cell Non-Hodgkin Lymphoma in People Living with HIV (PLWH) Treated in Australia: An Australasian Lymphoma Alliance Study
Authors: Lim Kenneth JC , Di Ciaccio Pietro , Hamad Nada , Polizzotto Mark N. , Milliken Sam , Cochrane Tara , Goh Zhong , Shaw Briony , Perry Evelyn , Gilbertson Michael , Kermode William , Cheah Chan Yoon , Latimer Maya , Ku Matthew 
Published: November 2021

Abstract
Background
Modern antiretroviral therapy (ART) has reduced HIV associated morbidity and mortality, and allowed a similar treatment approach of aggressive lymphomas in PLWH to that of their HIV negative counterparts. Australia is an ethnically diverse country with a low HIV prevalence and an excellent population-wide ART coverage and adherence in PLWH. We aimed to describe the real-world Australian experience in managing PLWH diagnosed with diffuse large B cell lymphoma (DLBCL) and Burkitt lymphoma (BL), and compare our treatment approach and outcomes against international data.
Methods
This was a retrospective, multicenter study conducted by the Australasian Lymphoma Alliance across 6 centers in 5 states. HIV positive patients with biopsy proven BL and DLBCL, diagnosed between 1st January 2009 and 31st December 2019 were identified through each institution's database. Baseline patient and disease characteristics, treatment exposure and outcomes were extracted from hospital medical records. Descriptive statistics, and survival analyses were performed as appropriate.
Results
44 patients (24 DLBCL, 20 BL) were included in the analysis. The median age was 52 years (range 32-78). The median follow-up was 1.8 years (range 0.1-13.1). 36 (82%) patients presented with advanced stage (III-IV) disease. 28 (64%) were defined as high-risk based on disease specific IPI scoring systems. The mean CD4 count was 334 cells/μL at diagnosis and 10 (23%) patients had a CD4 count of &lt;100 cells/μL. 23 (52%) had a HIV viral load &lt;50 copies/ml. 12 (27%) were diagnosed with HIV at the time of lymphoma diagnosis (Mean CD4 count 191 cells/μL, mean viral load 665,612 copies/ml). 41 (93%) patients received chemotherapy with curative intent and 39 (88%) received Rituximab. 37 (84%) were given concurrent ART and chemo(immuno)therapy. 11 (55%) of BL patients were treated with CODOX-M/IVAC or HyperCVAD followed by 6 (30%) with Da-EPOCH. 14 (58%) of DLBCL patients received CHOP-based therapy with 11 (45%) receiving more intensive regimens (Da-EPOCH, HyperCVAD or CODOX-M/IVAC). In the whole cohort, median number of chemotherapy cycles delivered was 6, 6, 4 and 3 for CHOP, Da-EPOCH, CODOX-M/IVAC and HyperCVAD respectively. CR rates after first-line curative intent therapy were 75% and 83% in BL and DLBCL respectively. All treatment response assessments were made by positron emission tomography. Grade 3-4 toxicity was significant higher in patients receiving intensive chemotherapy (77% vs 29%, p=0.015). Total treatment related mortality was 5% (2 died of bacterial sepsis). The 2-year OS was 77% (95% CI 61-88); 67% for BL (95% CI 46-88) and 81% for DLBCL (95% CI 53-90)]. 2-year PFS was 67% for BL (95% CI 40-83) and 77% for DLBCL (95% CI 53-89). An initial drop of mean CD4 count post treatment was observed (334 to 214 cells/μL), followed by a rise after 6 and 12 months (290 and 431 cells/μL respectively) (fig 1). At 6 months post chemotherapy, 83% of patients had a HIV viral load of &lt;50 copies/ml with 40% and 83% achieving a CD4 count of &gt;350 cells/μL and &gt;200 cells/μL respectively.
Conclusions
A significant proportion of PLWH still present with aggressive lymphoma as an AIDS-defining event prior to HIV diagnosis, despite high levels of health education and healthcare availability. Our results appear equivalent to those for non-HIV patients with acceptable toxicity. Current Australian practice favors treating aggressive lymphomas in PLWH similarly to the HIV negative population, with the addition of concurrent ART. CD4+ T-cell-related immune reconstitution appears to recover within 6 months post-therapy. The OS of this cohort appears similar to the HIV negative population and published cohort studies (Coutinho AIDS 2013, Evens Blood 2019, Alderuccio Blood Adv 2021).
Figure 1 Figure 1.

Disclosures
Hamad: Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Cheah: Beigene: Consultancy, Honoraria, Other: advisory; Celgene: Research Funding; AstraZeneca: Consultancy, Honoraria, Other: advisory; Loxo/Lilly: Consultancy, Honoraria, Other: advisory; TG Therapeutics: Consultancy, Honoraria, Other: advisory; AbbVie: Research Funding; Roche: Consultancy, Honoraria, Other: advisory and travel expenses, Research Funding; Janssen: Consultancy, Honoraria, Other: advisory; MSD: Consultancy, Honoraria, Other: advisory, Research Funding; Gilead: Consultancy, Honoraria, Other: advisory; Ascentage pharma: Consultancy, Honoraria, Other: advisory. Ku: Genor Biopharma: Consultancy; Antegene: Consultancy; Roche: Consultancy.