A retrospective observational study on cutaneous adverse events induced by immune checkpoint inhibitors.

BACKGROUND: Cutaneous adverse events (CAEs) related to oncological therapies are a common scenario in daily clinical practice. METHODS: This is a retrospective observational study collecting the data regarding CAEs of patients treated with immune checkpoints inhibitors (ICIs) in four different Italian centers. RESULTS: Of 323 patients included, 305 were evaluable for this analysis; 182 patients (59.7%) had metastatic cutaneous melanoma (CM), 99 (32.5%) non-small cell lung cancer (NSCLC) and 24 (7.8%) renal cell carcinoma (RCC). The most frequent CAEs that we found, considering all the 305 patients, were pruriginous maculopapular rash (10.2% of the patients), vitiligo-like areas (7.2% of the patients), psoriasiform rash (6.2% of the patients), asymptomatic maculopapular rash (4.6% of the patients), and lichenoid rash (4.3% of the patients). Vitiligo-like areas occurred more frequently in patients with CM, while a lichenoid rash was more frequently observed in patients with RCC. Treatment interruption was related to drug-induced CAEs in 15.4% of melanoma patients and 0.0% of lung and kidney patients. Patients developing a cutaneous adverse event had better overall response rate and higher progression free survival and overall survival than the patients without CAEs. CONCLUSIONS: Our study brings new information on the characteristics of CAEs related to ICIs treatment in three different types of cancers, CM, NSCLC and RCC.

Cutaneous side effects and types of dermatological reactions in metastatic melanoma patients treated by immunotherapies or targeted therapies: A retrospective single center study.

Immunotherapy and target therapy have revolutionized treatment of stage III/IV melanoma. Both treatments show a favorable toxicity profile even if cutaneous adverse events (AEs) are frequent (30%-40% of cases). This is a retrospective single center cohort study that included patients with stage IV or inoperable stage III metastatic melanoma (AJCC 8th) who received BRAFi + MEKi therapy or immunotherapy with Checkpoint inhibitors. All cutaneous AEs were ascertained by a dermatologist based on clinical and histological findings. The primary outcome was to provide a detailed clinical dermatological classification of cutaneous adverse events and an evaluation of the incidence of skin toxicity in the two arms of therapy (immunotherapy and target therapy). A total of 286 patients with stages III-IV metastatic melanoma were included: 146 received immunotherapy and 140 target therapy. In the immunotherapy cohort, 63 (43.1%) cutaneous reactions were observed while 33 skin reactions (23.6%) were identified in patients treated with target therapy. All the skin toxicities observed were grade I, excepted four cases: an erythema multiforme-like eruption, a grade III psoriasis and two grade III maculopapular rashes. Immunotherapy in older age resulted statistically related to skin toxicities (p = 0.011), meanly in metastatic setting (p = 0.011). Cumulative incidence of skin toxicities was 65.63% in immunotherapy cohort (p = 0.001). Also multivariate logistic regression shows a significant association between skin adverse events and immunotherapy (odds ratio [OR] = 0.50; 95% confidence interval [CI]: 0.29-0.85, p: 0.01) and between cutaneous AEs and metastatic setting (OR = 1.97; 95% CI: 1.04-3.74, p: 0.04). We have also shown that as the age of initiation of therapy increases the probability of developing skin toxicity grows. However, stratifying by type of therapies the effect of age persists only in immunotherapy (OD: 1.04; CI: 1.01-1.06; p: 0.04) while for target therapy age does not affect the onset of skin toxicity (OD 1.01; CI 0.98-1.04; p = 0.42). No differences were shown between patients on target therapy and immunotherapy regarding gender. Patients were also evaluated regarding concomitant therapies and seems that Levotyroxine may be involved in AEs during immunotherapy treatment. More studies are needed to deepen this aspect, also considering the medical history and diverse drug associations. Cutaneous adverse events are characterized by heterogeneous manifestations, are more often seen in patients on immunotherapy and dermatologists can play a crucial role in multidisciplinary care.