Immune-checkpoint inhibitors to treat cancers in specific immunocompromised populations: a critical review

Abstract

Because of their efficacy against numerous cancers, immune-checkpoint inhibitors (ICIs), anti-cytotoxic T-lymphocyte antigen-4, and anti-programmed cell death monoclonal antibodies are being used ever more often in oncology. However, some patients were excluded from clinical trials because of their comorbidities despite their potentially higher cancer frequencies, as is the case for immunocompromised patients. Areas covered: We analyzed reported preclinical and clinical information and evaluated the risk/benefit ratio for four immunocompromised populations: people living with human immunodeficiency virus (PLHs), solid-organ transplant recipients, recipients of hematopoietic stem-cell allografts, and patients with autoimmune diseases. Expert commentary: Information available in the literature is fragmentary and scarce, making it difficult to evaluate the risk/benefit ratio. It can, nonetheless, be noted that ICI use in PLHs seems possible. For solid-organ transplant recipients, the risk for the graft seems elevated. For the other two populations, it is difficult to conclude at this time.

Real-World Clinical and Economic Outcomes in Selected Immune-Related Adverse Events Among Patients with Cancer Receiving Immune Checkpoint Inhibitors

“…This differs from clinical trials, from which these patients have largely been excluded [14], although several studies suggest that patients with underlying autoimmune disease can be successfully treated with ICIs if patients are closely monitored and managed [21][22][23][24]. Evidence on the successful use of ICI treatment in patients with immunocompromised conditions is lacking, with one study suggesting possibly increased graft risk among patients who had solid organ transplants [25]. Patients in the current study who experienced an irAE had a somewhat higher average number of immune-related or immunecompromised comorbid conditions in the previous 6 months compared with those without an irAE.…”

Immune Checkpoint Inhibitors in Transplantation—A Case Series and Comprehensive Review of Current Knowledge

“…However, in clinical practice, oncologists had to deal with cases of SOTR with chemotherapy-refractory cancer for whom ICI appeared as the only therapeutic option. Publications of individual cases and small series since 2015 and subsequent meta-analyses 7,8,42,[51][52][53][54][55] provided a preliminary overview of the risk and efficacy of ICI management in SOTR. For example, in several studies, it is now clear that SOTR treated with anti-PD-1 are at higher risk of transplant rejection than patients treated with anti-CTLA-4, 7,51,56 although nonsignificantly in some recent meta-analyses.…”

“…This literature analysis and others 7,8,42,[51][52][53][54][55] provide an overview of the benefit and risk associated with ICI use in cancer management in transplantation. ICI are a useful tool in cancer management than can rarely be left aside in the setting of solid organ transplantation despite the risk of rejection.…”

Smokers or non-smokers: who benefits more from immune checkpoint inhibitors in treatment of malignancies? An up-to-date meta-analysis

“…Immune checkpoint inhibitors (ICIs), including PD-1/PD-L1 and CTLA-4 inhibitors, are monoclonal antibodies that remove tumor cells by activating T lymphocytes and enhancing immune response [1]. In 2010, a phase III randomized controlled clinical trial (RCT) [2] confirmed that ipilimumab, a CTLA-4 inhibitor, significantly improved overall survival (OS) in patients with metastatic melanoma compared with traditional vaccine therapy.…”