Editorial : Management of immune-related adverse events for patients undergoing treatment with checkpoint inhibitors

Immunotherapy with immune checkpoint inhibitors has emerged as the most significant advance in the treatment of cancer in recent years and has revolutionized cancer management (1). Until recently, it had been assumed that the immune system was not effective in protecting humans against the development of neoplastic diseases. Checkpoints inhibitors are co-receptors expressed by T cells. These co-receptors regulate T cell activation negatively and play a central role in the maintenance of peripheral self-tolerance. Co-inhibitory receptor ligands are significantly expressed in a variety of malignancies resulting in evasion of anti-cancer immunity. These molecules include programmed cell death protein 1 (PD-1) and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and were discovered by Tasuku Honjo and James P. Allison in 1992 and 1996, respectively (2, 3). These scientists were jointly awarded the 2018 Nobel Prize for Physiology or Medicine in recognition of this ground-breaking research. Monoclonal antibodies targeting the CTLA-4 and PD-1 and their ligands have produced significant clinical responses against a variety of malignancies (4). FDA registered checkpoint inhibitors include pembrolizumab (5), nivolumab (6), cemiplimab (7), atezolizumab (8), darvolumab (9) and avelumab (10) for numerous indications including melanoma, lung cancer (small and non-small cell types), bladder cancer, Hodgkin’s disease and others (5–10). Other co-inhibitory molecules under research include T cell immunoglobulin and mucin domain-containing molecule-3 (TIM-3) (11), Lymphocyte activation gene-3 (LAG-3) (12), V-domain Ig-containing Suppressor of T cell Activation (VISTA) (13), and B- and T-lymphocyte attenuator (BTLA) (14). Treatment with antibodies inhi biting immune checkpoints are well-tolerated by the vast majority of patients and are less toxic compared to standard anticancer chemotherapy agents. These immune side-effects are referred to as immune-related adverse events (IrAE) (15).http://www.frontiersin.org/Oncologyam2019Immunolog

Recent advances, patient selection & challenges in managing cancer patients undergoing treatment with immune checkpoint inhibitors

This editorial is published on the occasion of World Cancer day - February 4, 2022.Cancer immunotherapy with humanized monoclonal antibodies (mAbs) that target co-inhibitory immune checkpoint molecules (ICMs) is the most meaningful advance in the management of malignant diseases in recent years. This has coincided with the acquisition of eloquent, cutting edge insights into the molecular mechanisms, which regulate cell–cell interactions that are fundamental to maintain a balanced, well-synchronized human immune system. These developments have also revitalized the practice of immunotherapy, especially the realization of novel immunomodulatory therapeutic modalities that have the potential to restore weakened anti-cancer immune responses.The Cancer Association of South Africa and the National Research Foundation of South Africa.https://journals.lww.com/ijmr/pages/default.aspxam2023Immunolog

Dermatologic immune-related adverse events : the toxicity spectrum and recommendations for management

Immune checkpoint inhibitors are a new class of oncologic drugs that act via the inhibition of check- points, thereby unlocking the immune system to attack cancer cells. Their emergence has radically changed the concept of therapy in oncologic patients. However, despite their overall favorable profile, their use has been associated with specific toxicities that may potentially affect treatment. The so-called immune-related adverse events (irAEs) mostly correspond to dysimmune reactions that can affect nearly every organ system, in theory, notably with the development of colitis, hepatitis, pneumonitis, or thy- roiditis. Dermatologic irAEs are also among the most common, reaching a rate of approximately 40%. They are characterized by a wide phenotypic range, including mainly eczematous or lichenoid rashes, psoria- sis, or autoimmune bullous disorders. Pruritus may accompany the aforementioned rashes or develop as an isolated symptom without the presence of skin changes. Depigmentation and hair/nail changes can be also observed in association with immune checkpoint inhibitor treatment. In the current article, we present an overview of the clinical spectrum of irAEs and provide tips for early recognition and manage- ment of dermatologic irAEs. We highlight the role that dermatologists can play in relieving patients and allowing for oncologic treatment to be maintained and administered more safely.The Cancer Association of South Africa and the National Research Foundation of South Africa.https://www.sciencedirect.com/journal/international-journal-of-womens-dermatologyam2022Immunolog

MASCC 2020 recommendations for the management of immune-related adverse events of patients undergoing treatment with immune checkpoint inhibitors

Oncoimmunotherapy with immune checkpoint inhibitor–targeted antibodies has developed as the most significant advance in the management of cancer in recent years. The concept that the immune system was unsuccessful in protecting humans against the development of cancer has changed over the last decade. Checkpoint molecules are inhibitory (PD-1, PDL-1, CTLA-4, TIM-3, LAG-3, BTLA, and HEVM) and stimulatory (CD27, CD40, OX40, GITR, ICOS, and CD137) co-receptors expressed mostly by T cells, but also by other immune cells including antigen-presenting dendritic cells. The basic function of these inhibitory co-receptors is to negatively regulate T cell activation, which is critical in the maintenance of peripheral self-tolerance. The co-inhibitory receptor ligands for these immune checkpoint molecules are, however, also significantly upregulated in various types of cancers, resulting in evasion of anticancer immunity.The Cancer Association of South Africa (CANSA) and the National Research Foundation (NRF) of South Africa.http://link.springer.com/journal/5202021-09-04hj2020Immunolog

Meta-analysis comparing incidence of grade 3-4 neutropenia with ALK inhibitors and chemotherapy in patients with non-small-cell lung cancer

AIM : This meta-analysis compared incidence of grade 3-4 neutropenia with ALK inhibitors versus chemotherapy in patients with non-small-cell lung cancer. MATERIALS AND METHODS : PubMed/MEDLINE was searched to identify Phase II and III randomized clinical trials published up to 25 October 2018. Summary incidence, relative risk and corresponding 95% CIs were calculated for grade 3-4 neutropenia. RESULTS : Five randomized clinical trials were included. Relative risk (95% CI) of developing grade 3-4 neutropenia with ALK inhibitor versus chemotherapy was 0.27 (0.07-1.06). Probabilities of developing grade 3-4 neutropenia were 6.56 and 14.19%, respectively; no significant difference was found. CONCLUSION : In patients with non-small-cell lung cancer, incidence of grade 3-4 neutropenia with ALK-targeted therapy is not significantly different compared with chemotherapy.This meta-analysis was funded by Hexal AG, Holzkirchen, Germany. B Rapoport has received grants from Sandoz, personal fees from Amgen South Africa, Roche Malaysia, Teva and Cipla South Africa.https://www.futuremedicine.com/loi/fonhj2019Immunolog

Tuberculosis infection in a patient treated with Nivolumab for non-small cell lung cancer : case report and literature review

Nivolumab (PD-1 inhibitor) and other immune checkpoint inhibitors are used primarily to promote reactivation of anti-tumor immunity. However, due to their generalized immunorestorative properties, these agents may also trigger an unusual spectrum of side-effects termed immune-related adverse events. In the case of the lung, pulmonary infiltrates in patients treated with the anti-PD-1 inhibitors, nivolumab, or pembrolizumab, especially patients with non-small cell lung cancer, can result from immune-related pneumonitis, which, until fairly recently was believed to be of non-infective origin. This, in turn, may result in progression and pseudo-progression of disease. An increasing body of evidence has, however, identified pulmonary tuberculosis as an additional type of anti-PD-1 therapy-associated, immune-related adverse event, seemingly as a consequence of excessive reactivation of immune responsiveness to latentMycobacteriumtuberculosis infection. The current case report describes a 56-year old Caucasian female who presented with microbiologically-confirmed tuberculosis infection while on nivolumab therapy for non-small cell lung cancer. Notably, the patient, seemingly the first described from the African Continent, had not received immunosuppressive therapy prior to the diagnosis of tuberculosis.http://www.frontiersin.org/Oncologyam2020Immunolog

A case report of post-radiotherapy c-MYC-positive angiosarcoma of the breast

Angiosarcoma of the breast is an unusual malignancy and carries a poor prognosis, with a 5-year overall survival rate ranging from 27 to 48%. Radiotherapy-induced angiosarcoma (RIAS) of the breast is very uncommon, with an estimated incidence of 1 in 1,000 cases of breasts treated with radiotherapy for breast cancer. The increase in radiotherapy usage may lead to an increased incidence of RIAS. A case presentation of a 67-year-old patient with tubular adenocarcinoma of the left breast who developed c-MYC-positive RIAS of the breast is presented. The patient was successfully treated with surgery. We presented a classic case of c-MYC RIAS. c-MYC was reported to be positive in RIAS and other types of angiosarcomas. Clinical examination and early detection of RIAS breast angiosarcoma is vital to improving outcomes in these patients.The Cancer Association of South Africa (CANSA) and the National Research Foundation (NRF) of South Africa.https://www.karger.com/CROam2023Immunolog

Treatment of infections in cancer patients : an update from the neutropenia, infection and myelosuppression study group of the Multinational Association for Supportive Care in Cancer (MASCC)

INTRODUCTION : Patients with hematological and advanced solid malignancies have acquired immune dysfunction, often exacerbated by treatment, posing a significant risk for the development of infections. This review evaluates the utility of current clinical and treatment guidelines, in the setting of management of infections in cancer patients. AREAS COVERED : These include causes of infection in cancer patients, management of patients with high-risk and low-risk febrile neutropenia, management of low-risk patients in an outpatient setting, the role of granulocyte colony-stimulating factor (G-CSF) in the prevention and treatment of neutropenia-related infections, management of lung infections in various clinical settings, and emerging challenges surrounding the risk of infection in cancer patients treated with novel treatments. The literature search was performed by accessing PubMed and other databases, focusing on published clinical trials of relevant anti-cancer agents and diseases, primarily covering the recent past, but also including several key studies published during the last decade and, somewhat earlier in a few cases. EXPERT REVIEW : Notwithstanding the promise of gene therapy/gene editing in hematological malignancies and some types of solid cancers, innovations introduced in clinical practice include more discerning clinical management such as the generalized use of biosimilar formulations of G-CSF and the implementation of novel, innovative immunotherapies.The Cancer Association of South Africa (CANSA) and the National Research Foundation (NRF) of South Africa.http://tandfonline.com/toc/ierj20hj2022Immunolog

Emerging challenges in the evaluation of fever in cancer patients at risk of febrile neutropenia in the era of COVID-19 : a MASCC position paper

Patients with cancer are at higher risk of more severe COVID-19 infection and have more associated complications. The position paper describes the management of cancer patients, especially those receiving anticancer treatment, during the COVID-19 pandemic. Dyspnea is a common emergency presentation in patients with cancer with a wide range of differential diagnoses, including pulmonary embolism, pleural disease, lymphangitis, and infection, of which SARS-CoV-2 is now a pathogen to be considered. Screening interviews to determine whether patients may be infected with COVID-19 are imperative to prevent the spread of infection, especially within healthcare facilities. Cancer patients testing positive with no or minimal symptoms may be monitored from home. Telemedicine is an option to aid in following patients without potential exposure. Management of complications of systemic anticancer treatment, such as febrile neutropenia (FN), is of particular importance during the COVID-19 pandemic where clinicians aim to minimize patients’ risk of infection and need for hospital visits. Outpatient management of patients with low-risk FN is a safe and effective strategy. Although the MASCC score has not been validated in patients with suspected or confirmed SARS-CoV-2, it has nevertheless performed well in patients with a range of infective illnesses and, accordingly, it is reasonable to expect efficacy in the clinical setting of COVID-19. Risk stratification of patients presenting with FN is a vital tenet of the evolving sepsis and pandemic strategy, necessitating access to locally formulated services based on MASCC and other national and international guidelines. Innovative oncology services will need to utilize telemedicine, hospital at home, and ambulatory care services approaches not only to limit the number of hospital visits but also to anticipate the complications of the anticancer treatments.http://link.springer.com/journal/520hj2022Immunolog