Body composition and checkpoint inhibitor treatment outcomes in advanced melanoma: a multicenter cohort study

Introduction The association of body composition with checkpoint inhibitor outcomes in melanoma is a matter of ongoing debate. In this study, we aim to add to previous evidence by investigating body mass index (BMI) alongside CT derived body composition metrics in the largest cohort to date. Method Patients treated with first-line anti-PD1 +/- anti-CTLA4 for advanced melanoma were retrospectively identified from 11 melanoma reference centers in The Netherlands. Age, sex, Eastern Cooperative Oncology Group performance status, serum lactate dehydrogenase, presence of brain and liver metastases, number of affected organs and BMI at baseline were extracted from electronic patient files. From baseline CT scans, five body composition metrics were automatically extracted: skeletal muscle index, skeletal muscle density, skeletal muscle gauge, subcutaneous adipose tissue index and visceral adipose tissue index. All predictors were correlated in uni- and multivariable analysis to progression-free, overall and melanoma-specific survival (PFS, OS and MSS) using Cox proportional hazards models. Results A total of 1471 eligible patients were included. Median PFS and OS were 8.8 and 34.8 months, respectively. A significantly worse PFS was observed in underweight patients (multivariable HR=1.87, 95% CI 1.14-3.07). Furthermore, better OS was observed in patients with higher skeletal muscle density (multivariable HR=0.91, 95% CI 0.83-0.99) and gauge (multivariable HR=0.88, 95% CI 0.84-0.996), and a worse OS with higher visceral adipose tissue index (multivariable HR=1.13, 95% CI 1.04-1.22). No association with survival outcomes was found for overweightness or obesity and survival outcomes, or for subcutaneous adipose tissue. Discussion Our findings suggest that underweight BMI is associated with worse PFS, whereas higher skeletal muscle density and lower visceral adipose tissue index were associated with better OS. These associations were independent of previously identified predictors, including sex, age, performance status and extent of disease. No significant association between higher BMI and survival outcomes was observed. ### Competing Interest Statement AvdE has advisory relationships with Amgen, Bristol Myers Squibb, Roche, Novartis, MSD, Pierre Fabre, Sanofi, Pfizer, Ipsen, Merck and has received research study grants not related to this paper from Sanofi, Roche, Bristol Myers Squibb, Idera and TEVA and has received travel expenses from MSD Oncology, Roche, Pfizer and Sanofi and has received speaker honoraria from BMS and Novartis. JdG has consultancy/advisory relationships with Bristol Myers Squibb, Pierre Fabre, Servier, MSD, Novartis. GH has consultancy/advisory relationships with Amgen, Bristol-Myers Squibb, Roche, MSD, Novartis, Sanofi, Pierre Fabre and has received research grants from Bristol-Myers Squibb, Seerave. With all payments to the Institution. PJ has a research collaboration with Philips Healthcare. MBS has consultancy/advisory relationships with Pierre Fabre, MSD and Novartis. EK has consultancy/advisory relationships with Bristol Myers Squibb, Delcath and Lilly, , and received research grants not related to this paper from Bristol Myers Squibb, Delcath, Novartis and Pierre Fabre. All paid to the institution. PD has consultancy/advisory relationships with Paige, Visiopharm, Sectra, Pantarei and Samantree paid to the institution and research grants from Pfizer, none related to current work and paid to institute. KS has advisory relationships with Pierre Fabre, AbbVie and Sairopa and received research funding from Bristol Myers Squibb, TigaTx, Philips and Genmab. TL has received research funding from Philips. PM is employed at Quantib. DP has advisory relationships with Novartis, Pierre Fabre en BMS and honorarium for lecturing from Novartis. Not related to current work. All remaining authors have declared no conflicts of interest. ### Funding Statement This research was funded by The Netherlands Organization for Health Research and Development (ZonMW, project number 848101007) and Philips. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The Medical Ethics Committee "NedMec" waived ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data produced in the present work is not available due to confidentiality agreements.