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Use of Immune Checkpoint Inhibitors is Safe and Effective in Patients with Cancer and HIV Even in Those on Antiretroviral Therapy

May 26, 2023

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In a retrospective study conducted by the Cancer Therapy Using Checkpoint Inhibitors in People Living With HIV-International (CATCH-IT) Consortium, 390 patients with cancer and HIV received immune checkpoint inhibitors (ICIs) while on antiretroviral therapy, including 30% of patients with baseline CD4-positive T-cell counts <200 cells/µL. ICIs were deemed safe and had differential activity across tumour types.

Among patients with non–small cell lung cancer (NSCLC) and HIV, clinical outcomes were not generally influenced by CD4-positive T-cell counts or antiretroviral therapy regimens. In a subset of patients with metastatic NSCLC and HIV, the safety and activity of ICIs were comparable with a matched cohort of patients without HIV after matching for relevant clinical variables at the same institution. The findings are published by Dr. Abdul Rafeh Naqash of the Stephenson Cancer Center, University of Oklahoma in Oklahoma City, OK, US, and colleagues on 16 May 2023 in the JCO.

The authors wrote in the background that people with HIV remain at higher risk than those without HIV for developing various cancers. Since patients with HIV may have dysfunctional immune systems, there have been safety and efficacy concerns of including them in clinical studies with ICIs. Consequently, these studies have either entirely excluded patients with HIV or limited their participation to specific inclusion criteria such as baseline CD4-positive T-cell counts ≥350 cells/μL, HIV viral load <400 copies/mL, and adherence to antiretroviral therapy.

However, recent clinical studies and retrospective studies that included patients with HIV demonstrated that ICIs were active and safe, although these observations were hampered by small sample sizes and heterogeneous tumour types. Larger real-world cohorts are needed to address the existing knowledge gaps, guide clinical decision making, and increase treatment opportunities for this population.

The CATCH-IT Consortium assembled a real-world international cohort of patients with advanced cancer and HIV who received anti–PD-1- or anti–PD-L1-based therapies and evaluated the safety and activity. Kaplan-Meier method was used to estimate overall survival (OS) and progression-free survival (PFS). Objective response rates (ORRs) were measured per RECIST v1.1 or other tumour-specific criteria, whenever feasible. Restricted mean survival time was used to compare OS and PFS between matched patients with and without HIV with metastatic NSCLC.

Among 390 patients, median age was 58 years, 85% were males, 36% were Black, 70% received anti–PD-1/anti–PD-L1 monotherapy. Most common cancers were NSCLC (28%), hepatocellular carcinoma (HCC, 11%), and head and neck squamous cell carcinoma (HNSCC, 10%). In total 70% had CD4-positive T-cell counts ≥200 cells/µL, and 94% had HIV viral load <400 copies/mL.

The CATCH-IT Consortium investigators reported that 20% had any grade immune-related adverse events (irAEs) and 7.7% had grade ≥3 irAEs. The ORRs were 69% in patients with non-melanoma skin cancer, 31% in patients with NSCLC, 16% in patients with HCC, and 11% in patients with HNSCC. In the matched cohort of patients with metastatic NSCLC, comprising 61 patients with HIV and 110 without HIV, 20% of those with HIV and 22% without HIV had irAEs. Adjusted 42-month restricted mean survival time difference was –0.06 months (95% confidence interval [CI] –5.49 to 5.37; p = 0.98) for PFS and 2.23 months (95% CI –4.02 to 8.48; p = 0.48) for OS.

The authors concluded that in this large real-world cohort of patients with HIV receiving ICIs for various cancer types, they build on prior efforts and demonstrate that these patients have no excess or unexpected irAEs compared with historical and matched controls without HIV. In addition, this study adds a breadth of safety data to recently reported clinical studies of ICIs in patients with HIV that had considerably smaller sample sizes.

The investigators overcame some of previous limitations by including in this cohort the patients with more than 10 distinct cancer types, baseline CD4-positive T-cell counts <200 cells/μL, baseline HIV viral load ≥400, or opportunistic infections. The data also support the extension of the safety signal to treatment regimens that remain unexplored in prospective studies, such as the combination of ICIs with chemotherapy or targeted agents.

Furthermore, the authors showed that CD4-positive T-cell counts remained stable with modest changes in HIV viral load below the clinical significance threshold (<400 copies/mL) even when patients with HIV received the combination of anti–PD-1 and anti–CTLA-4 therapy. These data provide real-world evidence and support the findings of the currently ongoing AIDS Malignancy Consortium 095 clinical study where there was only a modest increase in plasma HIV RNA in patients with HIV receiving the combination of nivolumab and ipilimumab.

Overall, these results add to the growing body of evidence supporting the use of ICIs among patients with HIV to enhance their inclusion in ICI clinical studies. Similar to matched cohort analysis in metastatic NSCLC in this study, future studies comparing large, matched cohorts of patients with HIV and other cancer types are warranted for formal comparisons with the general population. International registry offers a unique opportunity for additional real-world subanalyses of clinical outcomes of patients with HIV receiving ICIs that could guide oncologists treating this unique population while awaiting results from ongoing ICI clinical studies.

The study was previously presented in part at the ASCO Annual Meeting (Chicago, IL, US, 3-7June 2022) and the Society for Immunotherapy of Cancer Annual Meeting (Boston, MA, US, 8-12 November 2022).