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

Alice Indini,Francesco Grossi,Erika Rijavec,Gianluca Tomasello,Michele Ghidini,Donatella Gambini,Barbara Galassi,Francesca Barbin,Monica Cattaneo,Claudia Bareggi

doi:10.3390/ijms22052628

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.

Highlights

We evaluated the association between body mass index (BMI) and survival outcomes of cancer patients receiving immune-checkpoint inhibitors (ICIs), and we focused on the incidence of treatment-related adverse events
We included eligible studies according to the following inclusion criteria: (1) studies reporting data of patients diagnosed with solid tumors and treated with ICIs, either as a single agent or in combination; (2) studies reporting data on BMI, either categorized into groups according to cutoff values, or as a continuous variable; (3) studies reporting data on disease response, and survival outcomes
There is a strong rationale for a correlation of excess adiposity with cancer prognosis

Summary

Introduction

Immunotherapy with immune-checkpoint inhibitors (ICIs) has demonstrated to provide survival benefit in a growing number of cancer patients. Antibodies targeting the programmed cell death 1 (PD-1), its ligand (PD-L1), and the cytotoxic T lymphocyteassociated antigen 4 (CTLA-4), are approved for the treatment of several solid tumors [1,2,3,4,5,6,7,8,9,10]. Despite the recognized efficacy of ICIs, still most patients receiving immunotherapy will experience treatment resistance (either primary, adaptive, or acquired), and eventually progress and die for cancer [11]. It is known that ICIs0 resistance is a heterogeneous phenomenon, which comes as the result of a complex interplay among the host immune system, cancer cells, and tumor microenvironment [11,12]. Several components contribute to the onset of treatment resistance, and most of them are largely unknown

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Conclusion