New research involving people living with HIV treated with immune checkpoint inhibitors has provided valuable insights into the safety and efficacy of immunotherapy in this historically excluded population, according to data published in the Journal of Clinical Oncology.1 The real-world data analysis builds on prior efforts,2 which demonstrated no excess or unexpected treatment-related immune toxicities compared with historical and matched controls without HIV.
“People living with HIV have been excluded from clinical trials of immune checkpoint inhibitors due to concerns about potential immune-related adverse events,” co–lead author Talal El Zarif, MD, a research fellow in oncology at Dana-Farber Cancer Institute, Boston, told The ASCO Post. “This study provides evidence that people living with HIV may receive the same standard of care as the general population. However, there is a need for further research to determine the safety and efficacy of these drugs in this patient population, particularly among patients with low CD4 counts,” he added.
Talal El Zarif, MD
Abdul Rafeh Naqash, MD
Although recent efforts have been made to include people living with HIV in immune checkpoint inhibitor clinical trials, there remains a paucity of real-world data on the use of these agents in this historically excluded population, according to senior author Abdul Rafeh Naqash, MD, Assistant Professor of Medicine at Stephenson Cancer Center, University of Oklahoma, Oklahoma City.
“Up to 74% of clinical trials involving immune checkpoint inhibitors excluded people living with HIV between 2019 and 2020,” Dr. Naqash told The ASCO Post.
For this study, researchers retrospectively analyzed 390 people living with HIV who had been treated with anti–PD-1– or anti–PD-L1–based immunotherapy across 10 distinct cancer types, with various baseline CD4-positive T-cell counts and HIV viral loads. Data were obtained from the Cancer Therapy Using Checkpoint Inhibitors in People Living With HIV–International (CATCH-IT) consortium established at the Dana-Farber Cancer Institute and included 33 additional institutions across the United States, Europe, and Australia. People living with HIV were included in the overall cohort if they (1) had a laboratory-confirmed diagnosis of HIV, (2) had a biopsy-proven solid or hematologic malignancy, and (3) received at least one dose of immune checkpoint inhibitor–based therapy between January 1, 2015, and October 1, 2021.
The primary endpoint of the study was overall survival, and secondary endpoints were immune-related adverse events and progression-free survival. Objective response rates were measured using Response Evaluation Criteria in Solid Tumors version 1.1 (for solid tumors), Lugano classification (for Hodgkin lymphoma and non-Hodgkin lymphoma), and AIDS clinical trials group criteria (for Kaposi sarcoma).
No Excess or Unexpected Toxicities
Co–lead author Elio Adib, MD, of Brigham and Women’s Hospital, reported that the incidence of immune-related adverse events of any grade was 20%. Objective response rates were 69% for nonmelanoma skin cancer, 31% for non–small cell lung cancer, 16% for hepatocellular carcinoma, and 11% for head and neck squamous cell carcinoma.
Elio Adib, MD
Amin H. Nassar, MD
Amin H. Nassar, MD, a third co–lead author of the study, emphasized that people living with HIV had no excess or unexpected treatment-related immune toxicities compared with historical and matched control patients without HIV.
“These findings revealed that people living with HIV experienced immune-related adverse events similar to those described in the general population,” said Dr. Nassar, a hematology/oncology fellow at Yale University, New Haven, Connecticut. “Importantly, the study demonstrated that the 24-month incidence rate of immune-related adverse events of any grade in people living with HIV with CD4-positive T-cell counts below 200 cells/mL was comparable to [that for] people living with HIV with CD4-positive T-cell counts above 200 cells/mL.”
Dr. Nassar added: “These data support the removal of arbitrary CD4 cutoffs when using immune checkpoint inhibitors for treating people living with HIV and reducing barriers to immune checkpoint inhibitor access based on their favorable benefit-to-risk profiles.”
Although these findings add to the growing body of evidence supporting the inclusion of patients with HIV in clinical studies involving anti–PD-1 and anti–PD-L1 therapies, the researchers also acknowledged some limitations. According to senior author Guru P. Sonpavde, MD, Medical Director of GU Oncology at the AdventHealth Cancer Institute, Orlando, Florida, these limitations include the inability to monitor trends in HIV viral load (to assess the impact of immune checkpoint inhibitors on the HIV reservoir) and missing data on some tumor-specific biomarkers.
These findings may lead to improved treatment options and better quality of life for people living with HIV as well as various cancer types, but Drs. El Zarif and Naqash underscored the need for additional research involving large, matched cohorts of people living with HIV and other cancer types to formally compare the outcomes with those of the general population.
“These findings highlight the importance of multidisciplinary care and further research to better understand the role of the immune system in treatment outcomes for people living with HIV and cancer,” the authors concluded.
DISCLOSURE: Dr. El Zarif and Dr. Naqash reported no conflicts of interest. Dr. Adib has a family member that had been employed by Amgen. Dr. Nassar has received grant/research support from PRIME Center and Veterans Health Administration; and has received honoraria from Tempus and OncLive. Dr. Sonpavde’s spouse is employed by Myriad Genetics; has received honoraria from UpToDate; has served as a consultant or advisor to Genentech, Merck, Janssen, Bristol Myers Squibb, Exelixis, EMD Serono, Astellas Pharma, Bicycle Therapeutics, Pfizer, Seagen, Gilead Sciences, Scholar Rock, G1 Therapeutics, Loxo/Lilly, Infinity Pharmaceuticals, Syapse, Lucence, Servier, and Vial; has served on speakers bureaus for Physicans’ Education Resource, OncLive, Research To Practice, Medscape, Gilead Sciences, Seagen, Natera, Exelixis, and Informação Brasileira de Oncologia; has received institutional research funding from Sanofi, AstraZeneca, Gilead Sciences, QED Therapeutics, Bristol Myers Squibb, Predicine, EMD Serono, and Jazz Pharmaceuticals; has been reimbursed for travel, accommodations, or other expenses from Bristol Myers Squibb; and has reported other relationships with Bristol Myers Squibb, Astellas Pharma, QED Therapeutics, Elsevier, Mereo BioPharma, and G1 Therapeutics.
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. May 16, 2023 (early release online).
2. El Zarif T, Nassar A, Adib E, et al: Safety and efficacy of immune checkpoint inhibitors in patients living with HIV and metastatic non-small cell lung cancer. 2022 SITC Annual Meeting. Abstract 437. Presented November 9, 2022.