Safety and Activity of Immune Checkpoint Inhibitors in People Living With HIV and Cancer: A Real-World Report From the Cancer Therapy Using Checkpoint Inhibitors in People Living With HIV-International (CATCH-IT) Consortium

Abstract

PURPOSE Compared with people living without HIV (PWOH), people living with HIV (PWH) and cancer have traditionally been excluded from immune checkpoint inhibitor (ICI) trials. Furthermore, there is a paucity of real-world data on the use of ICIs in PWH and cancer. METHODS This retrospective study included PWH treated with anti–PD-1- or anti–PD-L1-based therapies for advanced cancers. Kaplan-Meier method was used to estimate overall survival (OS) and progression-free survival (PFS). Objective response rates (ORRs) were measured per RECIST 1.1 or other tumor-specific criteria, whenever feasible. Restricted mean survival time (RMST) was used to compare OS and PFS between matched PWH and PWOH with metastatic NSCLC (mNSCLC). RESULTS Among 390 PWH, median age was 58 years, 85% (n = 331) were males, 36% (n = 138) were Black; 70% (n = 274) received anti–PD-1/anti–PD-L1 monotherapy. Most common cancers were NSCLC (28%, n = 111), hepatocellular carcinoma ([HCC]; 11%, n = 44), and head and neck squamous cell carcinoma (HNSCC; 10%, n = 39). Seventy percent (152/216) had CD4+ T cell counts ≥200 cells/µL, and 94% (179/190) had HIV viral load <400 copies/mL. Twenty percent (79/390) had any grade immune-related adverse events (irAEs) and 7.7% (30/390) had grade ≥3 irAEs. ORRs were 69% (nonmelanoma skin cancer), 31% (NSCLC), 16% (HCC), and 11% (HNSCC). In the matched mNSCLC cohort (61 PWH v 110 PWOH), 20% (12/61) PWH and 22% (24/110) PWOH had irAEs. Adjusted 42-month RMST difference was –0.06 months (95% CI, –5.49 to 5.37; P = .98) for PFS and 2.23 months (95% CI, –4.02 to 8.48; P = .48) for OS. CONCLUSION Among PWH, ICIs demonstrated differential activity across cancer types with no excess toxicity. Safety and activity of ICIs were similar between matched cohorts of PWH and PWOH with mNSCLC.

Treating Cancer in People With HIV

“…Cervical lymph node biopsy revealed Epstein-Barr virus (EBV)-positive mixed cellularity classical Hodgkin lymphoma (HL). Positron emission tomography-computed tomography (PET-CT) showed 18-fluorodeoxyglucose ( 18 FDG)-avid lymph nodes in the cervical, mediastinal, and retroperitoneal chains along with 18 FDG-avid masses within the lung parenchyma consistent with stage IV disease. He received six cycles of brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine (A 1 AVD) with a complete response on end-of-treatment PET-CT.…”

“…The disease relapsed 13 months later, and he received second-line chemotherapy followed by autologous hematopoietic stem-cell transplant with a complete response. The patient experienced fevers, night sweats, and fatigue along with new shortness of breath 6 months later, with PET-CT showing widespread 18 FDG-avid disease (Fig 1). Supraclavicular lymph node biopsy again revealed relapsed HL.…”

“…These HIV-related effects are not completely reversed by ART alone. 13 Mounting evidence, which includes two prospective clinical trials, a systematic review, and most recently an international retrospective study of 390 PWH and advanced cancer (in the accompanying article by El Zarif et al 18 ), convincingly shows that anti-PD-(L)1 agents are safe in patients with wellcontrolled HIV. [19][20][21] Comparisons between people with and without HIV receiving anti-PD-(L)1 therapies with CD4 1 T-cell counts <350 cells/mL have not shown significant differences in rates of immune-mediated adverse events.…”

“…However, the prospective and retrospective studies of these agents in PWH have shown efficacy across a range of expected cancer types (eg, non-small-cell lung cancer, head and neck cancer, and hepatocellular carcinoma). In a matched cohort of patients with metastatic non-small-cell lung cancer, El Zarif et al 18 showed that cancer outcomes were similar between people with and without HIV across CD4 1 T-cell counts, including <200 cells/mL. There is a notable lack of data specific to the efficacy of anti-PD-(L)1 agents in HIV-associated HL.…”

Advancing Truth in Oncology by Complementing Clinical Trials With Evidence From Clinical Practice

“…Thus, when patients ask the question as to whether or not a given approved therapy is right for them, it should be possible to find data from similar patients with the same conditions to determine the answer. Other efforts have shown the benefits of immunotherapy to specific subpopulations, such as in patients with melanoma or lung cancer with co-occurring kidney or liver dysfunction, or for patients with certain rare comorbid conditions . When there are multiple choices, this kind of information can be particularly important for patients and clinicians when determining the best available therapy.…”