Management of the Adverse Effects of Immune Checkpoint Inhibitors

Abstract

By increasing the activity of the immune system, immune checkpoint inhibitors (ICPI) can have adverse inflammatory effects, which are referred to as immune-related adverse effects (irAEs). In this review, we present the recommendations for the appropriate identification and treatment of irAEs associated with ICPI to increase the safety and effectiveness of therapy with these immuno-oncological drugs. Several guidelines to manage irAEs adopted by different American and European societies in the field of oncology were identified. A narrative review of the several strategies adopted to manage irAEs was performed. With close clinical surveillance, ICPI can be used even in patients who have mild irAEs. Moderate to severe events require early detection and appropriate treatment, particularly in patients with a history of transplantation or pre-existing autoimmune disease. In most cases, adverse reactions can be treated with the interruption of treatment and/or supportive therapy, which includes, in serious adverse reactions, the administration of immunosuppressants. The identification and treatment of irAEs in the early stages may allow patients to resume therapy with ICPI. This review is an instrument to support healthcare professionals involved in the treatment and monitoring of patients who are administered ICPI, contributing to the timely identification and management of irAEs.

Immune-checkpoint blockade of CTLA-4 (CD152) in antigen-specific human T-cell responses differs profoundly between neonates, children, and adults

“…41,42 In addition, several strategies like interruption of treatment and/or supportive therapy which include administration of immunosuppresants are adopted to manage irAEs. 43,44 Even though our data show that blockade of CTLA-4 did not further increase the proportion of multifunctional neonatal T-cells, the checkpoint blockade of CTLA-4 still significantly enhanced the numbers of individual cytokine producers as well as the frequency of responding T-cells and their proliferation, indicating CTLA-4 impinges on more than one pathway. 10,12,27,45,46 The accelerated expansion of neonatal T-cells upon CTLA-4 blockade (Figure 2) could boost the relative numbers of multifunctional T-cells in neonates to a much higher level than in adults.…”

Management of immune‐related adverse events in anti‐PD‐1‐treated patients with advanced cutaneous squamous cell carcinoma

“…An escalation of immunosuppressive treatment with infliximab and/or cyclophosphamide must be considered in corticosteroidrefractory pneumonitis. [7][8][9][10][11] Renal irAEs…”

Modulatory effects of gut microbiome in cancer immunotherapy: A novel paradigm for blockade of immune checkpoint inhibitors

“…Presently, the U.S. Food and Drug Administration (FDA) have authorized the consumption of some mAbs including: cemiplimab (Libtayo), pembrolizumab (Keytruda), avelumab (Bavencio), atezolizumab (Tecentriq), durvalumab (Imfinzi), and nivolumab (Opdivo) for targeting PD-1 and PD-L1 in cancer immunotherapy. [78][79][80] Also, ipilimumab (Yervoy) that targets the CTLA-4 was demonstrated to function synergistically with nivolumab to induce T-cell antitumor activity in melanoma and small lung cell carcinoma. 81 Despite the obvious efficacy of PD-L1, PD-1, and CTLA-4 suppression in cancer therapy, not all patients responded to these treatments.…”

“…These important findings opened the way to run several clinical trials exploiting mAbs targeting PD‐1, PD‐L1, and CTLA‐4 in cancer immunotherapy for different kinds of cancers. Presently, the U.S. Food and Drug Administration (FDA) have authorized the consumption of some mAbs including: cemiplimab (Libtayo), pembrolizumab (Keytruda), avelumab (Bavencio), atezolizumab (Tecentriq), durvalumab (Imfinzi), and nivolumab (Opdivo) for targeting PD‐1 and PD‐L1 in cancer immunotherapy 78‐80 . Also, ipilimumab (Yervoy) that targets the CTLA‐4 was demonstrated to function synergistically with nivolumab to induce T‐cell antitumor activity in melanoma and small lung cell carcinoma 81 .…”