title: Sarcopenic overweight is associated with early acute limiting toxicity of anti-PD1 checkpoint inhibitors in melanoma patients.
abstract: Little is known on factors predicting toxicity of anti-PD1 checkpoint inhibitors. Sarcopenic obesity is associated with increased acute toxicity of cytotoxic agents and targeted therapies. We explored whether body composition also influenced the occurrence of early acute limiting toxicity (ALT) of anti-PD1 in melanoma patients. This is a monocentric, retrospective study analyzing toxicity outcome in consecutive melanoma patients treated with nivolumab or pembrolizumab. Various parameters linked to the patient or the disease status have been analysed. Body mass index (BMI; kg/m2) and muscle mass using CT were measured prior to treatment initiation. Chi-squared test and Mann-Whitney's tests were used for the comparison of categorical and continuous variables respectively. Among 68 melanoma patients treated with anti-PD1 (47 pembrolizumab, 21 nivolumab), 38 (56%) patients had a BMI ≥ 25 kg/m2and 11 (16%) a BMI ≥ 30, while 13 (19%) had both sarcopenia and a BMI ≥ 25 kg/m2. For the 11 (16%) patients who experienced early ALT, the mean BMI was higher (27.9 versus 24.7 kg/m2; p = 0.04). Among the 32 female patients, sarcopenic overweight patients had a 6.5-fold increased risk of ALT (50 versus 7.7%; p = 0.01). Sarcopenic overweight is associated with more early ALT of anti-PD1 in melanoma patients.
authors.affiliation: Department of Medical Oncology, CERTIM Group, Cochin Port-Royal Hospital, AP-HP, University Paris Descartes, 123 Bd Port-Royal, 75 679, Paris Cedex 14, France.
authors.forename: Valentine
authors.initials: V
authors.lastname: Heidelberger
authors.affiliation: Department of Medical Oncology, CERTIM Group, Cochin Port-Royal Hospital, AP-HP, University Paris Descartes, 123 Bd Port-Royal, 75 679, Paris Cedex 14, France. francois.goldwasser@aphp.fr.
authors.forename: François
authors.initials: F
authors.lastname: Goldwasser
authors.affiliation: Department of Dermatology, CERTIM Group, Cochin Port-Royal Hospital, AP-HP, University Paris Descartes, 123 Bd Port-Royal, 75 679, Paris Cedex 14, France.
authors.forename: Nora
authors.initials: N
authors.lastname: Kramkimel
authors.affiliation: Department of Medical Oncology, CERTIM Group, Cochin Port-Royal Hospital, AP-HP, University Paris Descartes, 123 Bd Port-Royal, 75 679, Paris Cedex 14, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Jouinot
authors.affiliation: Department of Medical Oncology, CERTIM Group, Cochin Port-Royal Hospital, AP-HP, University Paris Descartes, 123 Bd Port-Royal, 75 679, Paris Cedex 14, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Huillard
authors.affiliation: Department of Medical Oncology, CERTIM Group, Cochin Port-Royal Hospital, AP-HP, University Paris Descartes, 123 Bd Port-Royal, 75 679, Paris Cedex 14, France.
authors.forename: Pascaline
authors.initials: P
authors.lastname: Boudou-Rouquette
authors.affiliation: Department of Dermatology, CERTIM Group, Cochin Port-Royal Hospital, AP-HP, University Paris Descartes, 123 Bd Port-Royal, 75 679, Paris Cedex 14, France.
authors.forename: Johan
authors.initials: J
authors.lastname: Chanal
authors.affiliation: Department of Medical Oncology, CERTIM Group, Cochin Port-Royal Hospital, AP-HP, University Paris Descartes, 123 Bd Port-Royal, 75 679, Paris Cedex 14, France.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Arrondeau
authors.affiliation: Department of Dermatology, CERTIM Group, Cochin Port-Royal Hospital, AP-HP, University Paris Descartes, 123 Bd Port-Royal, 75 679, Paris Cedex 14, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Franck
authors.affiliation: Department of Medical Oncology, CERTIM Group, Cochin Port-Royal Hospital, AP-HP, University Paris Descartes, 123 Bd Port-Royal, 75 679, Paris Cedex 14, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Alexandre
authors.affiliation: Department of Pharmacokinetics and Pharmacochemistry, CERTIM Group, Cochin Port-Royal Hospital, AP-HP, University Paris Descartes, 123 Bd Port-Royal, 75 679, Paris Cedex 14, France.
authors.forename: Benoît
authors.initials: B
authors.lastname: Blanchet
authors.affiliation: Department of Biochemistry and Molecular Biology, CERTIM Group, Cochin Port-Royal Hospital, AP-HP, University Paris Descartes, 123 Bd Port-Royal, 75 679, Paris Cedex 14, France.
authors.forename: Karen
authors.initials: K
authors.lastname: Leroy
authors.affiliation: Department of Dermatology, CERTIM Group, Cochin Port-Royal Hospital, AP-HP, University Paris Descartes, 123 Bd Port-Royal, 75 679, Paris Cedex 14, France.
authors.forename: Marie-Françoise
authors.initials: MF
authors.lastname: Avril
authors.affiliation: Department of Dermatology, CERTIM Group, Cochin Port-Royal Hospital, AP-HP, University Paris Descartes, 123 Bd Port-Royal, 75 679, Paris Cedex 14, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Dupin
authors.affiliation: Department of Dermatology, CERTIM Group, Cochin Port-Royal Hospital, AP-HP, University Paris Descartes, 123 Bd Port-Royal, 75 679, Paris Cedex 14, France.
authors.forename: Sélim
authors.initials: S
authors.lastname: Aractingi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects* / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000188:drug therapy*; D008875:Middle Aged; D000077594:Nivolumab; D050177:Overweight / Q000188:drug therapy; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors*; D012189:Retrospective Studies; D055948:Sarcopenia / Q000188:drug therapy; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D000077594:Nivolumab; C582435:pembrolizumab
keywords: Melanoma; Nivolumab; Obesity; Pembrolizumab; Sarcopenia; Toxicity