Setting the scene – a future ‘epidemic’ of immune-related adverse events in association with checkpoint inhibitor therapy

Abstract

Cancer immune therapy with checkpoint inhibitors (CPIs) has changed the landscape of treatment for a growing number of indications. These drugs are associated with a specific mechanism of action that has profound implications for both immunology and inflammatory disease. This article looks to set the scene covering the history of CPI therapy to date and outlining the likely future developments.

Il-2 in combination with immune checkpoints inhibitors as a promising approach for cancer immunotherapy: A literature review

“…Несмотря на выдающиеся успехи ИКТ-терапии, 50-80% пациентов с различными вариантами злокачественных новообразований не отвечает на данный вид иммунотерапии. К настоящему времени наибольшая эффективность достигнута при одновременном применении ипилимумаба и ниволумаба: 3-летняя общая выживаемость превыша-ет 60% для пациентов с метастатической меланомой [17,18]. Тем не менее, связанные с этой комбинацией нежелательные явления были зарегистрированы у 96,8% пациентов, 58,5% из которых были 3 и 4 степени, что привело к вынужденному прекращению лечения у 24,5% пациентов и одному смертельному исходу.…”

IL-2 in combination with immune checkpoints inhibitors as a promising approach for cancer immunotherapy: A literature review

“…Despite the outstanding success of ICT therapy, 50-80% of patients with various variants of malignancies do not respond to this type of immunotherapy. To date, the greatest efficacy has been achieved with the concomitant use of ipilimumab and nivolumab, with a 3-year overall survival rate exceeding 60% for patients with metastatic melanoma [17,18]. However, adverse events associated with this combination have been reported in 96.8% of patients, 58.5% of which were grade 3 and 4, resulting in forced treatment discontinuation in 24.5% of patients and one fatality.…”

Distinct circulating cytokine/chemokine profiles correlate with clinical benefit of immune checkpoint inhibitor monotherapy and combination therapy in advanced non‐small cell lung cancer

“…However, additional toxicities introduced by combination therapy are common, compromising the sustainable clinical benefit of the immunotherapy. [11][12][13] Inspired by the success of targeted therapies in the precision medicine era, biomarkers expected to predict efficacy of ICIs have been searched for in patients who respond to ICIs. The expression of the PD-L1 molecule in tumor cells or the tumor microenvironment (TME) is the first established biomarker for ICIs.…”

“…Many efforts have been put forth to increase the response rate to ICIs, such as combining ICIs with chemotherapy, radiotherapy, or other systemic treatments. However, additional toxicities introduced by combination therapy are common, compromising the sustainable clinical benefit of the immunotherapy 11–13 …”