Nationwide multidisciplinary consensus on the clinical management of Merkel cell carcinoma: a Delphi panel.

Merkel cell carcinoma (MCC) is a rare and highly aggressive cutaneous neuroendocrine carcinoma. The MCC incidence rate has rapidly grown over the last years, with Italy showing the highest increase among European countries. This malignancy has been the focus of active scientific research over the last years, focusing mainly on pathogenesis, new therapeutic trials and diagnosis. A national expert board developed 28 consensus statements that delineated the evolution of disease management and highlighted the paradigm shift towards the use of immunological strategies, which were then presented to a national MCC specialists panel for review. Sixty-five panelists answered both rounds of the questionnaire. The statements were divided into five areas: a high level of agreement was reached in the area of guidelines and multidisciplinary management, even if in real life the multidisciplinary team was not always represented by all the specialists. In the diagnostic pathway area, imaging played a crucial role in diagnosis and initial staging, planning for surgery or radiation therapy, assessment of treatment response and surveillance of recurrence and metastases. Concerning diagnosis, the usefulness of Merkel cell polyomavirus is recognized, but the agreement and consensus regarding the need for cytokeratin evaluation appears greater. Regarding the areas of clinical management and follow-up, patients with MCC require customized treatment. There was a wide dispersion of results and the suggestion to increase awareness about the adjuvant radiation therapy. The panelists unanimously agreed that the information concerning avelumab provided by the JAVELIN Merkel 200 study is adequate and reliable and that the expanded access program data could have concrete clinical implications. An immunocompromised patient with advanced MCC can be treated with immunotherapy after multidisciplinary risk/benefit assessment, as evidenced by real-world analysis and highlighted in the guidelines. A very high consensus regarding the addition of radiotherapy to treat the ongoing focal progression of immunotherapy was observed. This paper emphasizes the importance of collaboration and communication among the interprofessional team members and encourages managing patients with MCC within dedicated multidisciplinary teams. New insights in the treatment of this challenging cancer needs the contribution of many and different experts.

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Competing interests: PAA—received research funding from Bristol Myers Squibb, Roche-Genentech, Pfizer/Array, Sanofi; had a consultant role for Bristol Myers Squibb, Roche-Genentech, Merck Sharp & Dohme, Novartis, Merck Serono, Pierre-Fabre, Sun Pharma, Sanofi, Idera, Sandoz, 4SC, Italfarmaco, Nektar, Pfizer/Array, Lunaphore, Medicenna; participated to Advisory Board for Bristol Myers Squibb, Roche-Genentech, Merck Sharp & Dohme, Novartis, AstraZeneca, Immunocore, Boehringer-Ingelheim, Eisai, Regeneron, Daiichi Sankyo, Oncosec, Nouscom, Seagen, iTeos. PB—Advisory board or conference honoraria: Merck, Sanofi-Regeneron, Merck Sharp & Dohme, Sun Pharma, Angelini, Molteni, Bristol Myers Squibb, GSK, Nestlè. CC—Participation to scientific meetings provided by Novartis, Sun, Pierre-Fabre, Bristol Meyers Squibb; Advisory board participation Novartis, MSD. VCS—Participation to scientific meetings provided by Novartis, Sun, Pierre-Fabre, Bristol Meyers Squibb; Advisory board participation Merck-Serono, Pierre-Fabre, Novartis; Invited speaker: Pierre-Fabre, Novartis, Bristol Meyers Squibb. APDT—Advisory Boards Bayer, Roche, Novartis, PharmaMar. NF—Personal financial interest Advisory board: AAA, Merck, MSD, Novartis, Pfizer; Public speaking: AAA, Ipsen. Institutional financial interest Grant: Ipsen, AAA, Merck. Clinical trials (local PI): 4SC, Astellas, Beigene, Fibrogen, Incyte, Ipsen, MSD, Nucana. GG—Participation to board: Merck, Glaxo, Pharmamar, Novartis, Bayer, EISAI. MM—Honoraria for serving as a speaker from MSD, Roche, Bristol Myers Squibb (BMS), Sanofi, AstraZeneca, Amgen, Pierre Fabre, Eli Lilly, GlaxoSmithKline (GSK), Sciclone, Alfasigma, and Merck Serono; Personal fees for advisory boards from Merck Sharp & Dohme Corp., Roche, BMS, Incyte, AstraZeneca, Amgen, Pierre Fabre, Eli Lilly, Sanofi, GSK, Alfasigma, and Merck Serono; Stockholder in Epigen Therapeutics and Theravance. PQua—Invited speaker and advisory board participation: BMS, Merck, MSD; Novartis, Pierre Fabre, Sanofi, Roche. PQue—Advisory board participation: Roche, Novartis, Pierre Fabre, Merk Sharp and Dome, BMS, Sanofi, Sun Pharma, Merck. FS—Personal financial interests Advisory board, public speaking: Ipsen, Novartis, Pfizer, Advanced Accelerator Applications, Merck, Hutchison Medipharma Limited—Institutional financial interests Clinical trials (PI): GETNE, Incyte, MSD, Hutchison Medipharma Limited—Non financial interests AIOM: coordinator of neuroendocrine neoplasms guidelines, ITANET: executive board member ESMO: member of the NETs and endocrine tumors faculty Panelists MB reports honoraria for consulting, advisory role, speakers’ bureau, travel, accommodation, expenses from MSD, Roche/Genertech, AstraZeneca, Thermo Fisher Scientific, Illumina. FB reports participation to Advisory Klox Technologies, Smith And Nephew, Acelity 3m, Urgo Medical, Decomed, Mimedx. RB reports donors to the Hospital and/or participation to Advisory Boards AZ, BI, Novartis, MSD, Otsuka, Lilly, Roche, Amgen, GSK, Eisai. AB reports advisory board: Janssen, IPSEN, Novartis AAA, AMGEN - Public speaking: Novartis AAA, AMGEN. DC reports consultant/advisory role for Ipsen, Novartis, Pfizer, Advanced Accelerator Applications, Merck. FC reports advisory board or conference honoraria for BMS, MSD, Pierre Fabre, Novartis. RD reports participation as advisor and speaker for BMS, Novartis, MSD, Sanofi, Pierre Fabre. AMDG has served as a consultant and/or advisor to Incyte, Pierre Fabre, Glaxo Smith Kline, Bristol Myers Squibb, Merck Sharp Dohme, and Sanofi and has received compensated educational activities from Bristol Myers Squibb, Merck Sharp Dohme, Pierre Fabre and Sanofi. GF reports AbbVie Srl, Ag Global Event, Allmiral, Amgen, Atenapoli, Bb & C. Srl, Boehringer Ingelheim Italia Spa, Casa Di Cura Ruesh Spa, Collage Spa, Cosmetica Srl, Defhaforum Srl, Dialecticon Srl, Dynamico Education Srl, Editamed Srl, Edizioni Minerva Medica, Effetti Srl, Eli Lilly Italy Spa, F.C. Congressi Srl, Galderma Italia Spa, General Topica Srl, Havas Life Italy Srl, Havas Pr Milan Srl, Health Publishing, Healthware Group, Hippocrates Sintech Srl, Hps Health Publishing & Service Srl, Icim International Srl, Infomedica Srl, Intramed Comunication, Iqvia Solution Srl, Janssen Cilag Srl, La Fonderie, Ldv Srl, Leo Pharma Spa, Maghia Srl, Medica Editoria, Medicoop Vesevo, Mertz Pharma Italia Spa, Micom Srl, Non Solo Meeting Srl, Novartis Pharma Ag, Palazzo Della Salute Srl, Perrigo Italia Srl, Pierre Fabre Dermo Cosmetique, Plannig Congressi, Prex Srl, Qbggroup Srl, Sidemast Srl, Sifarma Spa con socio unico, Sifarma Spa, Sintesi Infomedica Srl, Tecniche Nuove Spa, Thenewway Srl, Triumph Italy Srl, Uvet Gbt Spa, Valetudo Srl, Vyvalife Srl, Vyvamed Srl, Winch ‐ Srl. MCF has served on advisory boards and received honoraria for lectures from Bristol Myers Squibb, Merck Sharp & Dohme, Novartis, Sanofi and Sun Pharma. MTF reports participation to scientific meetings provided by Novartis, Pierre-Fabre, Bristol Meyers, Lilly, AbbVie. FG received honoraria for speaker/advisory role from Servier, Eli Lilly, Iqvia, Merck Serono, Amgen and Bristol Myers Squibb. DG reports Pfizer, Ipsen, Merck. PG reports lecture fees and Advisory Board: AstraZeneca, Roche, Pfizer, MSD, Novartis, Eli Lilly, Boehringer Ingelheim, AMGEN. MG reports participation to scientific meetings provided by Merck Sharp & Dohme, Novartis, Sun, Pierre-Fabre, Bristol Meyers Squibb; advisory board participation for Pierre-Fabre, Novartis, Merck Sharp & Dohme, Bristol Meyers Squibb; invited speaker: Pierre-Fabre, Novartis, Merck Sharp & Dohme, Bristol Meyers Squibb. DM reports honoraria or Advisory Board for Novartis, Bayer HealthCare Pharmaceuticals, Pierre-Fabre, Sanofi Genzyme, MSD Italia S.r.l., Roche, Skyline Dx B.V. LM reports participation to board Astellas and Ipsen. AMM reports Novartis, BMS, MSD, Pierre Fabre, Gilead, Sunpharma, Merck’s, Sanofi. FM reports consultant in events organized by Bristol Meyers Squibb, MSD, Sanofi, Sunpharma, Novartis e Pierre-Fabre, honoraria for participation to events MSD, Sanofi, Sunpharma, Novartis e Pierre-Fabre, participation to meetings: Pharmar, BMS, Novartis - Advisory Board Bristol Meyers Squibb, MSD, Sanofi, Sunpharma, Novartis e Pierre-Fabre. GP reports invited speaker and advisory board participation: BMS, MSD, Incyte, Novartis, Pierre Fabre, Roche, Sanofi. GP reports AbbVie; Almirall; Janssen Cilag; Leo-Pharma; Merck Serono, Novartis, Pfizer, Pierre Fabre, Sanofi Genzyme. JP reports participation to advisory board BMS, MSD. NP reports Kyowa Kirin, Merck Serono, MSD, Novartis, Pierre Fabre, Recordati Rare Diseases, Sanofi, Takeda. FS reports lecture fees: BMS, Novartis, MSD, Pierre Fabre, Sun Pharma, Sanofi, Merck, advisory board: MSD, Novartis, Philogen, Sun Pharma. LT reports financial support with the following subjects with commercial interests in the health sector: Elekta, Igea Medical, Sun Farma, Sanofi, Roche, Molipharma, Nanobiotix AB, HNS GEC-ESTRO WG, AIRO. IZ reports Advisory Board or speakers fee from Novartis, Sanofi Genzyme, Sunpharma, Philogen, MSD, La Roche Posay, Biogena. GCAC, LA, GB, AB, PB, LB, VB, FB, AC, VF, FF, MG, CG, RM, PM, RP, FP, PP, LR, GR, PR, GR, ET, MCT, MT, MV, BV have declared no significant conflict of interest.