Comparative Analysis of Mature T-Cell and NK/T-Cell Lymphomas in Patients with and without HIV: Results from the NA-Accord and Complete Cohorts
Authors: Koh Min Jung , Merrill Mwanasha H. , Koh Min Ji , Stuver Robert N. , Alonso Carolyn D. , Foss Francine M. , Mayor Angel M. , Gill M. John , Epeldegui Marta , Cachay Edward , Thorne Jennifer E. , Silverberg Michael J. , Horberg Michael A. , Atlhoff Keri N. , Nijhawan Ank E. , McGinnis Kathleen A. , Rabkin Charles S. , Napravnik Sonia , Shen Changyu , Jain Salvia 
Published: November 2021

Abstract
Background: Clinicopathological characteristics and prognosis for patients with HIV (PWH) and T-cell lymphomas (TCLs) in the current antiretroviral therapy (ART) era remains unknown. The primary objective of this study was to determine outcomes of patients with mature T and NK/T-cell lymphomas with and without HIV (PWoH) in North America. A secondary objective was to define variations in the survival of patients with TCLs and AIDS-defining B-cell lymphomas (A-BCLs) in the presence of ART.
Methods: The study population included patients from two source populations, the NA-ACCORD (The North American AIDS Cohort Collaboration on Research and Design) and COMPLETE (Comprehensive Oncology Measures for Peripheral T-cell Lymphoma), both of which have been previously described. The NA-ACCORD collaborates with &gt;20 longitudinal cohorts of adults (aged ≥ 18 years) with HIV in the United States and Canada. Within the NA-ACCORD cohort, we included patients with a validated incidental diagnosis of mature T and NK/TCL (n=52) or the most common A-BCLs including Burkitt's lymphoma (n=101), diffuse large B-cell lymphoma (DLBCL, n=500) and primary CNS lymphoma (PCNSL, n=64) between 1996 and 2016. COMPLETE is a prospective, multicenter cohort study of patients with newly diagnosed incidental mature TCLs in the United States between 2010 and 2014. Of the 452 eligible patients, 450 were included for analysis after exclusion of two patients with HIV infection. Patients were followed from diagnosis to the first of death, loss to follow-up or administrative censoring at 5 years. Kaplan-Meier and log-rank tests were used to estimate and compare survival.
Results: At the time of TCL diagnosis, PWH were significantly younger than patients without HIV (PWoH) (49 years vs. 60 years respectively; p&lt;0.001). PWH were predominantly men (96% vs. 63%; p&lt;0.001), of white race (64% vs. 77%; p&lt;0.006), with chronic kidney disease (19% vs. 2.2%; p&lt;0.001) and with co-infections such as hepatitis B virus (13% vs. 0.9%; p&lt;0.001) and hepatitis C virus (19% vs. 1.1%; p&lt;0.001). Anaplastic large-cell lymphoma (ALCL, n=26) was the most common histological subtype within PWH relative to peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS, n=143) among PWoH. More than 92% of the patients within the NA-ACCORD cohort were on at least one class of ART during their cohort enrollment period. Median duration of ART prior to lymphoma diagnosis was 2.9 years (0.7-9.4) and comparable for patients with TCLs and A-BCLs. The median time from NA-ACCORD cohort enrollment to lymphoma diagnosis was 2.3 years (IQR: 0.3-5.9 years) for TCLs and comparable for patients with the A-BCL subgroups (2.8 years, IQR: 0.6-7.2 years; p=0.21).
At the end of the 5-year follow-up period, the survival probability since TCL diagnosis was markedly lower at 0.32 (95% confidence interval [CI]: 0.21-0.49) among PWH in contrast to 0.45 (95% CI: 0.41-0.51) for PWoH. Specifically, survival probability since ALCL diagnosis was distinctively lower at 0.23 (95% CI: 0.11-0.47) among PWH in contrast to 0.76 (95% CI: 0.66-0.87) for PWoH. Mortality following lymphoma diagnosis was elevated for PWH vs. PWoH even after adjusting for statistically significant baseline clinical characteristics such as age, race, and ALCL status in multivariate analysis (adjusted HR: 1.92; 95% CI: 1.27, 2.91). Among PWH with TCL, CD4 &lt;200 and viral load (VL) &gt;500 (n=10) was associated with a lower survival relative to those with counts &gt;200 and/or VL &lt;500 (n=12, p=0.031). Upon stratification of PWH into different calendar periods based on year of diagnosis (1996-1999 vs. 2000-2009 vs. 2010-2016), we observed an improvement in survival for all subgroups over time. Overall, among PWH, PCNSL had the worst median overall survival (3.8 months, 95% Cl: 2.0-7.2 months) followed by ALCL (10.6 months, 95% Cl: 2.1-33.4 months), DLBCL (15.6 months, 95% CI: 12.7-22.2 months) and Burkitt's lymphoma.
Conclusions: Our report based on two large observational cohorts in North America highlights poor outcomes for TCLs among PWH compared to PWoH. In addition, within the PWH group, our study is the first to delineate inferior survival for patients with ALCLs relative to DLBCL and Burkitt's lymphoma accentuating the need for novel therapies. However, the overall prognosis for these lymphomas among PWH has improved in the last two decades, particularly among those with CD4&gt;200, underscoring the impact of early and sustained ART.

Disclosures
Alonso: Merck: Research Funding. Foss: Kyowa: Honoraria; Acrotech: Honoraria, Speakers Bureau; Seattle Genetics: Honoraria, Speakers Bureau; Mallinckrodt: Honoraria; Daiichi Sankyo: Honoraria; Kura: Honoraria. Jain: Trillium Therapeutics, Inc: Research Funding; Acro Biotech, Inc: Research Funding; Abcuro, Inc: Research Funding.