Severe cutaneous adverse reactions induced by targeted anticancer therapies and immunotherapies

Abstract

With the increasing use of targeted anticancer drugs and immunotherapies, there have been a substantial number of reports concerning life-threatening severe cutaneous adverse reactions (SCARs), including Stevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug rash with eosinophilia and systemic symptoms, drug-induced hypersensitivity syndrome, and acute generalized exanthematous pustulosis. Although the potential risks and characteristics for targeted anticancer agent- and immunotherapy-induced SCAR were not well understood, these serious adverse reactions usually result in morbidity and sequela. As a treatment guideline for this devastating condition is still unavailable, prompt withdrawal of causative drugs is believed to be a priority of patient management. In this review, we outline distinct types of SCARs caused by targeted anticancer therapies and immunotherapies. Also, we discuss the clinical course, latency, concomitant medication, tolerability of rechallenge or alternatives, tumor response, and mortality associated with these devastating conditions. Imatinib, vemurafenib, and rituximab were the top three offending medications that most commonly caused SJS/TEN, while EGFR inhibitors were the group of drugs that most frequently induced SJS/TEN. For drug rash with eosinophilia and systemic symptoms/drug-induced hypersensitivity syndrome and acute generalized exanthematous pustulosis, imatinib was also the most common offending drug. Additionally, we delineated 10 SCAR cases related to innovative immunotherapies, including PD1 and CTLA4 inhibitors. There was a wide range of latency periods: 5.5–91 days (median). Only eight of 16 reported patients with SCAR showed clinical responses. Targeted anticancer drugs and immunotherapies can lead to lethal SCAR (14 deceased patients were identified as suffering from SJS/TEN). The mortality rate of TEN was high: up to 52.4%. The information compiled herein will serve as a solid foundation to formulate ideas for early recognition of SCAR and to discontinue offending drugs for better management.

Rapid recovery of postnivolumab vemurafenib-induced Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) syndrome after tocilizumab and infliximab administration

“…16 Second, the immune checkpoint inhibitors strongly provoked activation of CD8+ cytotoxic T cells, which are also the key cellular mediators in drug-induced skin toxicity. 17 High levels of IP-10/CXCL10 and MCP-1/ CCL2 plasma concentration, which were documented in our patient only at the onset, that is, in the active phase of DRESS, confirm this process. IP-10/CXCL10 with MCP-1/ CCL2 plays a significant role in CD8+ T cell recruitment and in leucocyte homing to inflamed tissues, exacerbating inflammation and causing substantial tissue damage.…”

Adverse Reactions of Targeted Therapy in Cancer Patients: A Retrospective Study of Hospital Medical Data in China

“…In this study, 61% patients who underwent a targeted therapy had ADR, which was lower than previous observations (18,19). In fact, the proportion of patients with ADR in this study was far more than 61%.…”

Stevens-Johnson Syndrome–Like Reaction After Exposure to Pembrolizumab and Recombinant Zoster Vaccine in a Patient With Metastatic Lung Cancer

“…SJS only rarely occurs 8 weeks following suspected drug exposure, but late onset in patients receiving immunotherapy has been reported. 6,8 The association of some anticancer drugs with rare life-threatening serious adverse events such as SJS has been anecdotally reported, but has not been systematically examined. 9 Pembrolizumab is usually a well-tolerated therapy for metastatic cancers.…”