Immune-Related Adverse Effects of Cancer Immunotherapy— Implications for Rheumatology

Cancer is characterized by a perturbed immune landscape. Inside tumor microenvironment, immune system is reprogrammed to facilitate tumor growth and survival rather than eliminating it. This immune evasive mechanism needs to be reversed to normal for effective anticancer therapeutic strategy. Immunotherapy has emerged as a novel strategy for redeployment of immune cells against cancer. However, they suffer in their efficacy, response rate and side effects. This necessitated us to turn toward natural repertoires which can act as a substitute to conventional immunotherapeutics. Beta glucan, a polysaccharide derived from mushroom, serves the role of immunomodulator inside tumor microenvironment. It acts as pathogen associated molecular pattern and bind to various pattern recognition receptors expressed on surface of immune cells thereby facilitating their activation and crosstalk. This result in resurgence of suppressed immune surveillance in the tumor milieu. In this review, we highlight in brief the advances and limitation of cancer immunotherapy. Alongside, we have discussed the detailed mechanistic principle and recent advances underlying restoration of immune functionality by beta glucan.

The prevalence of the musculoskeletal immune-related adverse events (irAEs) is probably underestimated, as most studies report only severe side effects. Our aim was to describe and characterize all musculoskeletal irAEs in a large cohort of patients treated with immune checkpoint inhibitors (ICI).

We conducted a retrospective study among patients who received ICI from 07/27/2014 to 05/08/2020 at the medical oncology department of the Institut Paoli-Calmettes, Marseille, France. All medical files were systemically reviewed by a rheumatologist who collected clinical features, time of occurrence, treatment regimen, irAEs management, course and outcomes. We also assessed tumor response 3 months after introduction of ICI, according to severity and treatments used to manage musculoskeletal irAEs.

Among 927 patients treated with ICI for a solid tumor, 118 patients (12.7%) presented a musculoskeletal irAE. Their median age was 66.5, 61% were male, and they mainly had a lung (57.6%) or urological cancer (27.1%). The most frequently involved ICI was an anti PD-1. Arthralgias and myalgias were the most frequent musculoskeletal irAEs (9.8%) and inflammatory rheumatic features were reported in 36 patients (3.9%) with elevated acute phase reactants and negative immunological markers. The median time of onset was 2 months (IC 95% 1.8; 2.7). Tumor response at 3 months did not differ according to musculoskeletal irAE severity, type of manifestation (arthralgias/myalgias versus inflammatory rheumatic features), pain patterns (mechanical versus inflammatory) or irAE treatments.

Musculoskeletal irAEs in this large cohort of patients treated with ICI were frequent (12.7%), mostly mild and well tolerated.

Glucocorticoids (GCs) are a pharmacological class of drugs widely used in oncology in both supportive and palliative settings. GCs differentially impact organs with immediate and long-term effects; with suppressive effect on the immune system anchoring their use to manage the toxicities of immune checkpoint inhibitors (ICIs).

In addition, GCs are often used in the management of symptoms related to cancer or chemotherapy and as adjuvants in the treatment of pain in the management of other. In the palliative setting, GCs, especially administered subcutaneously can be to assist in the control of nausea, dyspnea, asthenia, and anorexia-cachexia syndrome.

In this narrative review, we aim to summarize the role of GCs in the different settings (curative, supportive, and palliative) to help clinicians use these important drugs in their daily clinical practice with cancer patients.

Cancer immunotherapies are drugs that modulate the body's own immune system as an anticancer strategy. Checkpoint inhibitor immunotherapies interfere with cell surface binding proteins that function to promote self-recognition and tolerance, ultimately leading to upregulation of the immune response. Given the striking success of these agents in early trials in melanoma and lung cancer, they have now been studied in many types of cancer and have become a pillar of anticancer therapy for many tumor types. However, abundant upregulation results in a new class of side effects, known as immune-related adverse events (IRAEs). It is critical for the practicing radiologist to be able to recognize these events to best contribute to care for patients on checkpoint inhibitor immunotherapy. Here, we provide a comprehensive system-based review of immune-related adverse events and associated imaging findings. Further, we detail the best imaging modalities for each as well as describe problem solving modalities. Given that IRAEs can be subclinical before becoming clinically apparent, radiologists may be the first provider to recognize them, providing an opportunity for early treatment. Awareness of IRAEs and how to best image them will prepare radiologists to make a meaningful contribution to patient care as part of the clinical team.