Skin rash associated with combined cytotoxic chemotherapy and immunotherapy for cancer: A retrospective single-center case series

In recent years, the development of combination therapies with immune checkpoint inhibitors (ICIs) and cytotoxic anticancer drugs has radically changed the management of diverse malignancies and significantly improved patient outcomes. Several clinical trials have shown that skin rash caused by combination therapy with ICIs and cytotoxic drugs may be more frequent and severe than that developing after administration of ICIs alone or cytotoxic drug monotherapy. However, most reports provide little information on severity, treatment, post-diagnosis course, and recurrence of rashes on drug rechallenges. We aimed to describe the experience of skin rashes developing within 2 weeks from the first administration of combination therapy with ICIs and cytotoxic drugs in 11 patients visiting our dermatology department. This study included seven men and four women, and the patients' median age was 52 years. The primary disease was non-small-cell lung cancer in eight patients, cervical cancer in two patients, and esophageal cancer in one patient. Nine patients had a maculopapular rash and two patients developed erythema multiforme-like eruptions. The skin rash was often accompanied by extracutaneous symptoms, such as fever (n = 9), mucositis (n = 4), and liver dysfunction (n = 2). In all cases, the symptoms improved with topical steroid therapy alone, with no patients exhibiting severe symptoms requiring systemic steroids or immunosuppressive agents. In addition, when the causative drugs were re-administered after recovery from the rash, only two patients relapsed with accompanying systemic symptoms, and all patients except one were able to continue treatment using the same drug regimen. Although it was suggested that the rash caused by the combination therapy of ICIs and cytotoxic drugs may be more prominent than that caused by each agent alone, comprehensive judgment, including histopathological examination, may indicate the feasibility of continuing the treatment regimen for cancer.

Automated summary

Combination therapy with immune checkpoint inhibitors and cytotoxic anticancer drugs can cause more frequent and severe skin rashes compared to monotherapy. This study aimed to describe the experience of skin rashes in 11 patients who received combination therapy with immune checkpoint inhibitors and cytotoxic drugs within 2 weeks.