Efficacy, Safety Observed With Immunotherapy in Patients With HIV

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Patients with HIV and cancer who received immune checkpoint inhibitors (ICIs) had similar clinical outcomes to patients without HIV and did not show excess toxicity, according to a retrospective study published in the Journal of Clinical Oncology.¹

Among 390 patients who had cancers including non–small cell lung cancer (NSCLC), hepatocellular carcinoma (HCC), and head and neck squamous cell carcinomas, 20% had any grade immune-related adverse events (irAEs) and 7.7% had grade 3 or higher irAEs. Antitumor activity varied by cancer type, but in a matched cohort of patients with metastatic NSCLC with or without HIV, there was no significant difference in progression-free survival (PFS) and overall survival (OS).

People with HIV are at high risk of developing cancers that can be treated with ICIs, including lung cancer, which is the second-leading cause of cancer deaths in these patients. Patients with HIV have been excluded or limited in enrollment for ICI trials because of concerns of targeting the immune system in immunodeficient patients, so there are not sufficient data on ICIs in these patients.

Data were collected from 33 participating institutions across the United States, Europe, and Australia in the Cancer Therapy using Checkpoint Inhibitors in PWH-International (CATCH-IT) consortium. Patients with HIV and cancer who received ICI therapy between January 1, 2015, and October 1, 2021, were included, all of whom received treatment in a real-world setting.

The matched cohorts of patients with metastatic NSCLC with and without HIV were made at each participating institution on a 1:2 or 1:1 ratio. Patients were matched according to sex, 10-year age groups, class of ICI, use of concurrent chemotherapy, and number of prior lines of systemic therapy. There were 61 patients with HIV and 110 without HIV included.

The primary end point was OS with secondary end points including irAEs and PFS. Objective response rate (ORR) was also measured. A total of 390 patients were included in the safety analysis and 378 in the analysis of clinical outcomes. The most common cancer was NSCLC with 111 patients.

The median age was 58 years, and 331 patients (85%) were male. Thirty-six percent were Black and 14% were Hispanic. The majority (70%) received anti–PD-1/PD-L1 monotherapy. HIV was well controlled in 94%; 70% had a CD4+ T-cell count of at least 200 cells/mL, whereas 63% had CD4:CD8 ratio of at least 0.4.

In patients with NSCLC, the ORR was 31% overall; it was 38% in first-line therapy and 25% in the second line. There was no significant difference in OS or PFS based on CD4+ T-cell count at baseline, or in patients receiving integrase-strand transfer inhibitor as part of their antiretroviral therapy.

In 44 patients with HCC, 33 received nivolumab (Opdivo) and 11 received atezolizumab (Tecentriq) plus bevacizumab (Avastin). Patients with Child-Pugh class A had significantly better OS (P = .02) and PFS (P < .001) compared with patients with Child-Pugh class B disease, as well as an ORR of 24% versus 6.3%, respectively.

Patients with nonmelanoma skin cancer had an ORR of 69%, those with melanoma had an ORR of 47%, and those with head and neck squamous cell carcinomas had an ORR of 11%.

The 24-week cumulative incidence rate (CIR) of irAEs in the safety population was 15% (95% CI, 12%-19%). Hospitalization was required in 29 patients (7.4%). The most common grade 3 or higher irAEs were colitis/diarrhea or pneumonitis each occurring in 1.5% of patients. Steroids were administered in 39 out of 79 patients with irAEs, 21 of whom required high-dose glucocorticoids. One patient required immunosuppression with mycophenolate mofetil. Thirty-nine patients (12%) discontinued treatment because of irAEs. One death was attributed to ICI-related pneumonitis in a patient with small cell lung cancer.

The rate of any-grade and grade 3 or higher irAEs in those receiving ICI monotherapy or chemoimmunotherapy was similar to the full population, and lower in patients who received ICI plus targeted therapy. In those who received dual ICI therapy, 39% had any-grade irAEs and 13% had grade 3 or higher irAEs.

In patients with baseline CD4+ T-cell counts less than 200 cells/mL, the rate of any-grade irAEs was 16% and grade 3 or higher was 7.8%, compared with 24% and 9.9% in those with baseline CD4+ T-cell counts of at least 200 cells/mL. The CIR was not significantly different in these groups, but it was lower in patients with baseline CD4:CD8 ratio of less than 0.4.

HIV viral load was observed in patients who received nivolumab plus ipilimumab (Yervoy). In 7 out of 10 who had data available throughout treatment, viral load was undetectable, whereas 3 had a transient rise in viral load peaking at 63 copies/mL. Six patients had an active opportunistic infection at the time of initiation of ICI which did not worsen during treatment.

In the matched NSCLC cohorts, 24-month OS rate was 42.3% in patients with HIV versus 41.5% for those without HIV, and the 24-month PFS rates were 17.8% and 18.4%, respectively. The difference in restricted mean survival time within 42 months adjusted for race, performance status, histology, smoking status, and PD-L1 expression was 2.23 months (95% CI, -4.02 to 8.48; P = .48) for OS and -0.06 months (95% CI, -5.49 to 5.37; P =.98) for PFS between the groups. The ORR was 28% for those with HIV and 36% for those without HIV (P = .31).

The rate of irAEs was 20% in those with HIV and 22% in those without HIV, with grade 3 irAEs occurring at a rate of 12% and 9.1%, respectively. Systemic steroids were required for 9.8% of those with HIV and 15% of those without HIV.

“In this large real-world cohort of PWH receiving ICIs for various cancer types, we build on prior efforts and demonstrate that PWH have no excess or unexpected treatment-related immune toxicities compared with historical and matched controls without HIV,” the investigators stated in their report.

They noted that these data cover more cancer types and other factors that have not been examined in previous trials and retrospective data on HIV and ICIs. The inclusion of 64 patients with CD4+ T-cell count of less than 200 cells/mL enabled study of this underrepresented population and showed they did not have worse irAE outcomes.

The investigators recommended further research into specific biological factors and cancer but concluded that ICIs do not have worse safety and efficacy in patients with HIV. “Overall, these results add to the growing body of evidence supporting the use of ICIs among [people with HIV] to enhance their inclusion in ICI clinical studies,” they stated.

_Reference:

_{1. El Zarif T, Nassar AH, Adib E, et al. 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. J Clin Oncol. 2023;41(21):3712-3723. doi:10.1200/JCO.22.02459}