PMID- 35384181 OWN - NLM STAT- MEDLINE DCOM- 20220608 LR - 20231213 IS - 1529-8019 (Electronic) IS - 1396-0296 (Print) IS - 1396-0296 (Linking) VI - 35 IP - 6 DP - 2022 Jun TI - Cutaneous side effects and types of dermatological reactions in metastatic melanoma patients treated by immunotherapies or targeted therapies: A retrospective single center study. PG - e15492 LID - 10.1111/dth.15492 [doi] LID - e15492 AB - 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. CI - (c) 2022 The Authors. Dermatologic Therapy published by Wiley Periodicals LLC. FAU - Gullo, Giulia AU - Gullo G AD - Department of Medical Sciences, Dermatologic Clinic, University of Turin, Torino, Italy. FAU - Rubatto, Marco AU - Rubatto M AUID- ORCID: 0000-0003-1706-656X AD - Department of Medical Sciences, Dermatologic Clinic, University of Turin, Torino, Italy. FAU - Fava, Paolo AU - Fava P AD - Department of Medical Sciences, Dermatologic Clinic, University of Turin, Torino, Italy. FAU - Brizio, Matteo AU - Brizio M AD - Department of Medical Sciences, Dermatologic Clinic, University of Turin, Torino, Italy. FAU - Tonella, Luca AU - Tonella L AD - Department of Medical Sciences, Dermatologic Clinic, University of Turin, Torino, Italy. FAU - Ribero, Simone AU - Ribero S AUID- ORCID: 0000-0002-0098-1406 AD - Department of Medical Sciences, Dermatologic Clinic, University of Turin, Torino, Italy. FAU - Medri, Matelda AU - Medri M AD - Skin Cancer Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Meldola, Italy. FAU - Avallone, Gianluca AU - Avallone G AD - Department of Medical Sciences, Dermatologic Clinic, University of Turin, Torino, Italy. FAU - Mastorino, Luca AU - Mastorino L AUID- ORCID: 0000-0001-7386-3219 AD - Department of Medical Sciences, Dermatologic Clinic, University of Turin, Torino, Italy. FAU - Fierro, Maria Teresa AU - Fierro MT AD - Department of Medical Sciences, Dermatologic Clinic, University of Turin, Torino, Italy. FAU - Stanganelli, Ignazio AU - Stanganelli I AD - Skin Cancer Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Meldola, Italy. AD - Medicine and Surgery Department, University of Parma, Parma, Italy. FAU - Quaglino, Pietro AU - Quaglino P AD - Department of Medical Sciences, Dermatologic Clinic, University of Turin, Torino, Italy. LA - eng PT - Journal Article DEP - 20220510 PL - United States TA - Dermatol Ther JT - Dermatologic therapy JID - 9700070 RN - 0 (Immunologic Factors) SB - IM MH - Cohort Studies MH - *Drug-Related Side Effects and Adverse Reactions/etiology MH - Humans MH - Immunologic Factors/therapeutic use MH - Immunotherapy/adverse effects/methods MH - *Melanoma/drug therapy/pathology MH - Retrospective Studies MH - *Skin Diseases/etiology MH - *Skin Neoplasms/drug therapy/etiology MH - Melanoma, Cutaneous Malignant PMC - PMC9287008 OTO - NOTNLM OT - advanced melanoma OT - adverse events OT - cutaneous toxicity OT - immunotherapy OT - target therapy COIS- The authors declare no conflict of interest. EDAT- 2022/04/07 06:00 MHDA- 2022/06/09 06:00 PMCR- 2022/07/15 CRDT- 2022/04/06 09:15 PHST- 2021/11/22 00:00 [received] PHST- 2022/04/02 00:00 [accepted] PHST- 2022/04/07 06:00 [pubmed] PHST- 2022/06/09 06:00 [medline] PHST- 2022/04/06 09:15 [entrez] PHST- 2022/07/15 00:00 [pmc-release] AID - DTH15492 [pii] AID - 10.1111/dth.15492 [doi] PST - ppublish SO - Dermatol Ther. 2022 Jun;35(6):e15492. doi: 10.1111/dth.15492. Epub 2022 May 10.