Clinical Outcomes and Immunotoxicity in People with HIV (PWH) after Definitive Chemoradiation (CRT) for Anal Squamous Cell Carcinoma.

PURPOSE/OBJECTIVE(S): Anal cancer disproportionately affects PWH despite antiretroviral therapy. Data on CRT outcomes are limited. Modern IMRT CRT decreases acute toxicity but may exacerbate immune dysregulation from chronic HIV. Although historical CRT has been associated with prolonged CD4 count suppression, little is known about late immunotoxicity in PWH after contemporary CRT. We report clinical outcomes and long term immunotoxicity.

MATERIALS/METHODS: Single-center retrospective review of all PWH confirmed on chart review with anal squamous cell carcinoma without prior pelvic irradiation treated with definitive IMRT CRT. Patient and CRT factors including HIV suppression (<200 copies/mL), mean CD4 count (cells/µL), and receipt of capecitabine (C) or 5-fluorouracil (F) +/- mitomycin (M) were summarized with n (%) or median (interquartile range). Progression-free and overall survival (PFS; OS) were estimated per Kaplan-Meier with 95% confidence intervals and compared with log-rank tests. Mean CD4 count and CD4:CD8 were compared by HIV suppression status (Welch's t-test); longitudinal changes in median CD4 count and CD4:CD8 were compared between baseline vs. nadir (within 6 months of CRT start) and 1-year follow-up for patients with complete data (Wilcoxon signed-rank test).

RESULTS: A total of 23 PWH were treated between 2010-2022, median age 52, median 16 (13 - 19) years after HIV diagnosis; 4 had unsuppressed HIV; AJCC 8th stage I/II/III/IV 5/5/12/1. Radiation dose was median 54 Gy in 30 fractions over 42 (40 - 44) days. Most had C+M (57%); only 43% had 2×M with either C or F. One had neoadjuvant carboplatin/paclitaxel/pembrolizumab. With 2.9 (1.03 - 3.3) years follow-up, median OS was 6.6 (6.2 - unreached [UR]) years. With 2.2 (0.67 - 2.7) years follow-up, median PFS was UR. OS and PFS were similar regardless of HIV suppression status (both P ≥ 0.09). Overall baseline CD4 count was 458 (226 - 484), and CD4:CD8 was 0.54 (0.2 - 0.7). Nadir CD4 was 100 (59 - 126) and CD4:CD8 was 0.3 (0.2 - 0.4). Baseline and nadir CD4 count and CD4:CD8 were lower if HIV-unsuppressed (each P ≤ 0.04). One year after CRT, CD4 count was 252 (102 - 276), while CD4:CD8 was 0.5 (0.2 - 0.7). For 7 patients with repeated values the change in median from baseline to nadir, 6-, and 12-months post-CRT was -282, -549 (both P = 0.02), -480 (P = 0.9) for CD4 counts, and -0.7, -0.5, -0.4 (each P > 0.5) for CD4:CD8 ratios; none had unsuppressed HIV.

CONCLUSION: Definitive IMRT CRT with guideline-concordant doublet chemotherapy for anal cancer in PWH is effective despite unsuppressed HIV. Treatment leads to prolonged immunological changes that may increase the risk of HIV-related morbidity and mortality. Modifiable treatment-related causes of hematoimmunologic toxicity should be investigated further, and immune surveillance after CRT should be considered to better understand impact on quality of life.