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Association Between Body Mass Index and Survival Outcomes In Patients Treated With Immune Checkpoint Inhibitors: Meta-analyses of Individual Patient Data.

ABSTRACT: Despite that immune checkpoint inhibitors (ICIs) had tremendous improved the survival of multiple solid tumors, only a limited proportion of patients are responsive to ICIs. Therefore, effective variables are urgently needed to predict the probability of response to ICIs. Systematic searches were conducted from inception up to May, 2020. Prospective or retrospective studies of ICIs that investigated the association between body mass index (BMI) and survival outcomes, including overall survival (OS) and/or progression-free survival (PFS), were selected. The association between each BMI category and survival outcomes was calculated using Cox proportional hazard regression models and quantified as hazard ratio (HR) with corresponding 95% confidence interval. Seven clinical studies involving data from 3768 individual patients were included. The median OS was 15.5 months (95% confidence interval: 14.7-16.2 mo) and the median PFS was 5.7 months (5.2-6.3 mo). The median OS was significantly longer in overweight/obese patients than in nonoverweight patients (20.7 vs. 11.3 mo; P<0.001). The difference in OS between overweight and obese patients was not statistically significant (HR: 1.14, P=0.098). Similar results were observed for PFS outcomes. Subgroup analysis demonstrated improved OS in overweight/obese patients with nonsmall-cell lung cancer (HR: 0.81, P=0.002), melanoma (HR: 0.66, P<0.001), renal cell carcinoma (HR: 0.53, P<0.001), and multiple cancer type (HR: 0.34, P<0.001), with parallel results noted regarding PFS outcomes. Results of the present study suggested that BMI may be a satisfactory prognostic factor for patients treated with ICIs.

SUBMITTER: Nie RC

PROVIDER: S-EPMC8500279 | biostudies-literature | 2021 Nov-Dec 01

REPOSITORIES: biostudies-literature

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Association Between Body Mass Index and Survival Outcomes In Patients Treated With Immune Checkpoint Inhibitors: Meta-analyses of Individual Patient Data.

Nie Run-Cong RC Chen Guo-Ming GM Wang Yun Y Yuan Shu-Qiang SQ Zhou Jie J Duan Jin-Ling JL Liu Wen-Wu WW Chen Shi S Cai Mu-Yan MY Li Yuan-Fang YF

Journal of immunotherapy (Hagerstown, Md. : 1997) 20211101 9

Despite that immune checkpoint inhibitors (ICIs) had tremendous improved the survival of multiple solid tumors, only a limited proportion of patients are responsive to ICIs. Therefore, effective variables are urgently needed to predict the probability of response to ICIs. Systematic searches were conducted from inception up to May, 2020. Prospective or retrospective studies of ICIs that investigated the association between body mass index (BMI) and survival outcomes, including overall survival ( ...[more]

PMID: 34456293

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Project description:BACKGROUND:Recent evidence suggested a potential correlation between overweight and the efficacy of immune checkpoint inhibitors (ICIs) in cancer patients. PATIENTS AND METHODS:We conducted a retrospective study of advanced cancer patients consecutively treated with anti-PD-1/PD-L1 inhibitors, in order to compare clinical outcomes according to baseline BMI levels as primary analysis. Based on their BMI, patients were categorized into overweight/obese (≥ 25) and non-overweight (< 25). A gender analysis was also performed, using the same binomial cut-off. Further subgroup analyses were performed categorizing patients into underweight, normal weight, overweight and obese. RESULTS:Between September 2013 and May 2018, 976 patients were evaluated. The median age was 68 years, male/female ratio was 663/313. Primary tumors were: NSCLC (65.1%), melanoma (18.7%), renal cell carcinoma (13.8%) and others (2.4%). ECOG-PS was ≥2 in 145 patients (14.9%). PD-1/PD-L1 inhibitors were administered as first-line treatment in 26.6% of cases. Median BMI was 24.9: 492 patients (50.6%) were non-overweight, 480 patients (50.4%) were overweight/obese. 25.2% of non-overweight patients experienced irAEs of any grade, while 55.6% of overweight/obese patients (p < 0.0001). ORR was significantly higher in overweight/obese patients compared to non-overweight (p < 0.0001). Median follow-up was 17.2 months. Median TTF, PFS and OS were significantly longer for overweight/obese patients in univariate (p < 0.0001, for all the survival intervals) and multivariate models (p = 0.0009, p < 0.0001 and p < 0.0001 respectively). The significance was confirmed in both sex, except for PFS in male patients (p = 0.0668). CONCLUSIONS:Overweight could be considered a tumorigenic immune-dysfunction that could be effectively reversed by ICIs. BMI could be a useful predictive tool in clinical practice and a stratification factor in prospective clinical trials with ICIs.

Project description:BackgroundA male gender driven obesity paradox (improved survival for overweight/obese patients compared to normal weight) was recently shown in melanoma in the context of checkpoint inhibition (anti-PD-1/anti-CTLA4 monotherapy) in a pooled meta-analysis. We characterized the relationship of Body Mass Index (BMI) with survival and explored gender-based interactions with surrogates of body composition/malnutrition in the context of PD-1 blockade as monotherapy or in combination with ipilimumab in a real-world setting.MethodsAdvanced melanoma patients who received at least one dose of pembrolizumab, nivolumab, or nivolumab plus ipilimumab (combination) from June 2014 to September 2016 were included in this retrospective cohort study (N = 139). Overall Survival (OS) and Progression Free Survival (PFS) were the main outcomes. Analysis was performed using Random Survival Forests (RSF)/ multivariable Cox Proportional-Hazards models.ResultsOverweight/Class-I (25- < 35 kg/m2) obese patients had a significantly lower risk of mortality (adjusted-HR:0.26; 95%CI:0.1-0.71; p-value = 0.008) and progressive disease (adjusted-HR:0.43; 95%CI:0.19-0.95; p-value:0.038) compared to normal-weight (18.5- < 25 kg/m2). Class II/III obesity (compared to normal-weight) had an adjusted HR of 0.42 (95%CI: 0.1-1.77; p-value: 0.238) for OS and 1 (95%CI:0.34-2.94; p-value:0.991) for PFS. Exploration of interactions for OS showed that the association was predominantly driven by males (adjusted-HRmales:0.11; 95%CI:0.03-0.4; adjusted-HRfemales: 0.56; 95%CI:0.16-1.89; p-valueinteraction:0.044); the association was not seen in patients with serum creatinine< 0.9 mg/dL (adjusted-HR:0.43; 95%CI:0.15-1.24; p-valueinteraction:0.020), who were predominantly females. These observations were made in both the anti-PD-1 monotherapy (n = 79) and combination therapy (anti-PD-1/CTLA-4, n = 60) cohorts.ConclusionsThe findings support the existence of an "obesity paradox" restricted to overweight/Class-I obesity in the real-world setting; the association was driven predominantly by males who largely had higher serum creatinine levels, a surrogate for skeletal muscle mass in the setting of metastatic disease. These observations suggest that sarcopenia (low skeletal muscle mass) or direct measures of body mass composition may be more suitable predictors of survival in melanoma patients treated with PD-1 blockade (monotherapy/combination).

Project description:BackgroundRecent studies have reported that the combination of immune checkpoint inhibitors (ICIs) and antiangiogenic agents could be a promising therapeutic strategy for advanced non-small cell lung cancer (NSCLC). However, both ICIs and antiangiogenic agents are associated with endocrine dysfunctions, mainly hypothyroidism. The risk of hypothyroidism is potentially increased with the combination of ICIs and antiangiogenic agents. This study aimed to investigate the incidence and risk factors of hypothyroidism in patients receiving combination therapy.MethodsWe performed a retrospective cohort study of advanced NSCLC patients treated with ICIs and antiangiogenic agents at Tianjin Medical University Cancer Institute & Hospital from July 1, 2019, to December 31, 2021. Patients with normal thyroid function at baseline were enrolled, and information on the patients' characteristics before receiving combination therapy, including body mass index (BMI) and laboratory data, was obtained.ResultsAmong the 137 enrolled patients, 39 (28.5%) developed new-onset hypothyroidism, and 20 (14.6%) developed overt hypothyroidism. The incidence of hypothyroidism was significantly higher in obese patients than in patients with a low to normal BMI (P<0.001). Obese patients also had a higher incidence of overt hypothyroidism (P=0.016). Univariate logistic regression showed that BMI as a continuous variable was a significant risk factor for hypothyroidism [odds ratio (OR) 1.24, 95% confidence interval (CI): 1.10-1.42, P<0.001] and overt hypothyroidism (OR 1.17, 95% CI: 1.01-1.38, P=0.039). Multivariate logistic regression revealed that only BMI (OR 1.36, 95% CI: 1.16-1.61, P<0.001) and age (OR 1.08, 95% CI: 1.02-1.14, P=0.006) were significant risk factors for treatment-related hypothyroidism.ConclusionsThe risk of hypothyroidism in patients receiving a combination of ICIs and antiangiogenic therapy is manageable, and a higher BMI is associated with a significantly increased risk of hypothyroidism. Therefore, clinicians should be aware of the development of hypothyroidism in obese advanced NSCLC patients during the administration of ICIs combined with antiangiogenic agents.

Project description: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.

Project description:BackgroundImmune checkpoint inhibitors (ICIs) have improved survival outcomes in melanoma. Studies exploring the correlations between body mass index (BMI), type 2 diabetes (T2DM) and the outcomes of ICI treatment have yielded inconsistent results. In this study, we aim to investigate the effects of BMI and T2DM on survival outcomes of patients with melanoma receiving ICIs.MethodsA retrospective multicenter cohort of patients with melanoma treated with ICIs was analyzed. Overall survival was evaluated with Kaplan-Meier survival analysis, univariate Cox and multivariate Cox proportional hazards model. Propensity-score matching (1:1) analysis between overweight and non-overweight groups was done and survival analyses and Cox analyses were performed again. Subgroup analyses and secondary analyses stratifying patients with different weights and T2DM statuses were also performed.ResultsA total of 2,078 patients were included, of whom 1,412 were overweight (BMI≥25 kg/m2) and 666 were non-overweight (BMI<25 kg/m2). Overweight patients had better overall survival compared with non-overweight (median 71.7 vs 36.7 months, p<0.001). Patients with T2DM had worse overall survival compared with patients without T2DM (median 28.5 vs 67.3 months, p<0.001). After propensity-score matching (666 overweight were matched to 666 non-overweight), overweight patients remained to have better overall survival compared with non-overweight (median 67.7 vs 36.7 months, p<0.001). Patients with T2DM had worse survival in univariate Cox (HR 1.71, (95% CI: 1.20 to 2.43)) and multivariate Cox (HR 1.58, (95% CI: 1.08 to 2.31)) analyses. Overweight patients without T2DM had the best survival outcomes compared with other weight and T2DM combinations.ConclusionIn patients with melanoma treated with ICIs, being overweight had better survival outcomes compared with non-overweight. Having T2DM was associated with worse survival compared with those without T2DM. Further studies are needed to investigate the underlying mechanisms of these associations.

Dataset Information

Association Between Body Mass Index and Survival Outcomes In Patients Treated With Immune Checkpoint Inhibitors: Meta-analyses of Individual Patient Data.

Publications

Association Between Body Mass Index and Survival Outcomes In Patients Treated With Immune Checkpoint Inhibitors: Meta-analyses of Individual Patient Data.

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