Impact of BMI on Survival Outcomes of Immunotherapy in Solid Tumors: A Systematic Review

Abstract

Growing research has focused on obesity as a prognostic factor during therapy with immune-checkpoint inhibitors (ICIs). The role of body-mass index (BMI) in predicting response and toxicity to ICIs is not clear, as studies have shown inconsistent results and significant interpretation biases. We performed a systematic review to evaluate the relationship between BMI and survival outcomes during ICIs, with a side focus on the incidence of immune-related adverse events (irAEs). A total of 17 studies were included in this systematic review. Altogether, the current evidence does not support a clearly positive association of BMI with survival outcomes. Regarding toxicities, available studies confirm a superimposable rate of irAEs among obese and normal weight patients. Intrinsic limitations of the analyzed studies include the retrospective nature, the heterogeneity of patients’ cohorts, and differences in BMI categorization for obese patients across different studies. These factors might explain the heterogeneity of available results, and the subsequent absence of a well-established role of baseline BMI on the efficacy of ICIs among cancer patients. Further prospective studies are needed, in order to clarify the role of obesity in cancer patients treated with immunotherapy.

Cemiplimab in an Elderly Frail Population of Patients With Locally Advanced or Metastatic Cutaneous Squamous Cell Carcinoma: A Single-Center Real-Life Experience From Italy

“…Even with the limitations of the sample size, in the forest plot analysis, we did not find a correlation with response for other clinical features previously described as predictive markers, like male sex ( 35 ) and body mass index ( 36 ). We likewise found no differences in response between over or under the median age of 81 years.…”

Nutritional Status as a Predictive Biomarker for Immunotherapy Outcomes in Advanced Head and Neck Cancer

“…Whether or not patients who are obese and overweight confer an advantage remains controversial in the literature [ 20 , 21 , 22 , 23 , 24 , 25 , 26 ]. In fact, the literature on the predictive value of baseline BMI on immunotherapy response and survival show widely inconsistent results [ 33 ]. One possible reason for these controversial findings is that weight is a dynamic process and, especially during disease progression, a wider timeframe of serial measurements may reflect a more accurate representation of nutritional status in patients with late-stage disease.…”

The ambiguous role of obesity in oncology by promoting cancer but boosting antitumor immunotherapy

“…Although descriptions of the obesity paradox in lung cancer are not so mechanistically profound, epidemiological evidence is plenty. At least five different studies report a positive association between obesity (especially subcutaneous fat mass) and improved outcomes in patients receiving immune checkpoint inhibitors [ 414 ]. When compared to lean individuals, obese patients treated with pembrolizumab, nivolumab, or atezolizumab showed better and improved response to treatment, prolonged progression-free survival, and increased overall survival.…”

“…Apart from the beneficial aspects of obesity in cancer immunotherapy, the persistence of inflammation in obese patients has been linked to the development of irAEs [ 30 ]. Indeed, some studies associated higher BMI with increased risks of irAEs after immunotherapy [ 414 , 434 , 435 ]. In addition, limited evidence is available on the efficacy of immunotherapy upon obese and lean patients, which draws attention for considering BMI when designing randomized clinical trials for newer therapies [ 321 ].…”