Body mass index is not associated with survival outcomes and immune-related adverse events in patients with Hodgkin lymphoma treated with the immune checkpoint inhibitor nivolumab

Journal of Translational Medicine

Francesco D’Alò¹  Rosaria De Filippi²  Antonio Pinto³  Emanuela Morelli³  Luigi Rigacci⁴  Fortunato Morabito⁵  Armando Santoro⁶  Francesca Ricci⁶  Pier Luigi Zinzani⁷  Giovanni Tripepi⁸ 

[1] Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Roma, Italy;Dipartimento di Scienze Radiologiche ed Ematologiche, Università Cattolica del Sacro Cuore, Roma, Italy;Dipartimento di Medicina Clinica e Chirurgia, Università degli Studi Federico II, Napoli, Italy;Ematologia Oncologica e Trapianto di Cellule Staminali, Department of Hematology and Developmental Therapeutics, Istituto Nazionale Tumori, Fondazione ‘G. Pascale’, IRCCS, Via Mariano Semmola 49, 80131, Naples, Italy;Ematologia Oncologica e Trapianto di Cellule Staminali, Department of Hematology and Developmental Therapeutics, Istituto Nazionale Tumori, Fondazione ‘G. Pascale’, IRCCS, Via Mariano Semmola 49, 80131, Naples, Italy;Ematologia e Trapianto di Cellule Staminali, A.O. San Camillo Forlanini, Roma, Italy;Hemato-Oncology Department, Augusta Victoria Hospital, East Jerusalem, Israel;Unità di Ricerca Biotecnologica, Azienda Ospedaliera di Cosenza, Cosenza, Italy;Humanitas University, Milano, Italy;IRCCS Humanitas Research Hospital, Milano, Italy;IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia “Seràgnoli”, Bologna, Italy;Unità di Ricerca CNR-IFC, Reggio Calabria, Italy;

关键词: Hodgkin lymphoma;    Immune checkpoint inhibitors;    Body mass index;    Immune-related adverse events;   

DOI  :  10.1186/s12967-021-03134-4

来源: Springer

【 摘 要 】

BackgroundOverweight and obese patients with solid tumors receiving anti-programmed cell death-1 (PD-1)/PD-ligand-1(PD-L1) immune checkpoint inhibitors exhibit improved survival and higher risk of immune-related adverse events (irAEs) than those with a normal body mass index (BMI). In classic Hodgkin lymphoma (cHL), the impact of BMI on survival and immune-related toxicity is unknown. We evaluated for the first time associations of BMI with survival and irAEs in patients with relapsed/refractory (RR)-cHL undergoing PD-1 blockade.MethodsData from a multicenter study on 133 patients treated with the anti-PD1 antibody nivolumab (July 2015–December 2016) were retrieved from a prospective database. Progression-free (PFS), overall survival (OS), incidence and severity of irAEs according to BMI categories were estimated by Kaplan–Meier method, landmark-analyses and Cox regressions.ResultsPatients, mostly males (63%, n = 84) with a median age of 35 years (range, 15–82), advanced stage (75%), B symptoms (63%), bulky disease (24%), a median of 4 previous treatments (range, 1–9), received a median of 18 nivolumab doses (range, 1–57). No statistically significant differences across BMI subgroups emerged as to PFS, with 1-year rates of 67.1% for both normal weight (n = 66; 49.6%) and overweight (n = 31; 23.3%) patients. Underweight (n = 12; 9%) and obese (n = 24; 18%) patients had a 1-year PFS of 54.5% and 49%, respectively. In survival analyses, BMI either as a continuous (P = 0.5) or categorical (P for trend = 0.63) variable failed to associate with PFS. Response rates and time-to-response did not cluster in any BMI subset. No BMI-related differences in OS emerged across normal, overweight and obese patients but underweight patients had the worst survival. Occurrence of irAEs of whatever severity did not statistically associate with BMI.ConclusionsIn patients with RR-cHL receiving nivolumab, no statistically significant differences emerged in response rates, PFS and OS across BMI categories of normal weight, overweight and obese. Overweight/obese patients did not display an increased risk of irAEs. The exquisite sensitivity to anti-PD-1 antibodies, the unique cytokine milieu and effector pathways triggered by nivolumab in cHL, may represent biologic ‘equalizers’ counteracting the immunoregulatory effects of adiposity. Differently from solid tumors, BMI is not associated with treatment efficacy and immune-related toxicity and does not represent a predictive tool for PD-1-targeted immunotherapies in cHL.

【 授权许可】

CC BY