Related abstracts
Obesity as an Immune-Modifying Factor in Cancer Immunotherapy.
Canter RJ, Le CT, Beerthuijzen JMT, Murphy WJ.
J Leukoc Biol 2019;104(3):487–97.
Immunotherapy has achieved breakthrough status in many advanced stage malignancies and is rapidly becoming the fourth arm of cancer treatment. Although cancer immunotherapy has generated significant excitement because of the potential for complete and sometimes durable responses, there is also the potential for severe and occasionally life-threatening toxicities, including cytokine release syndrome and severe autoimmunity. A large body of work also points to a "metainflammatory" state in obesity associated with impairment of immune responses. Because immune checkpoint blockade (and other cancer immunotherapies) have altered the landscape of immunotherapy in cancer, it is important to understand how immune responses are shaped by obesity and how obesity may modify both immunotherapy responses and potential toxicities.
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Effect of excess weight and immune-related adverse events on the efficacy of cancer immunotherapy with anti-PD-1 antibodies.
Rogado J, Romero-Laorden N, Sanchez-Torres JM, et al.
Oncoimmunology 2020;9(1):1751548.
Immunotherapy is an effective treatment in advanced cancer, although predictors of response are limited. We studied whether excess weight influences the efficacy outcomes of immunotherapy. We have also evaluated the combined prognostic effect of excess weight and immune-related adverse events (irAEs). Efficacy of anti-PD-1 treatment was evaluated with both objective radiological response (ORR) rate and progression-free survival (PFS), and toxicity with irAEs. We studied the association between excess weight and ORR, PFS or irAEs. 132 patients diagnosed with advanced cancer were included. Median body mass index (BMI) was 24.9 kg/m2. 64 patients had normal weight (BMI<25 kg/m2), and 64 patients had excess weight (BMI≥25 kg/m2). Four patients had underweight and were excluded from further analysis. ORR was achieved in 50 patients (38.0%), median PFS was 6 months. 44 patients developed irAEs (33.3%). ORR was higher in excess weight patients than in patients with normal weight (51.6% vs 25.0%; OR 3.45, p = .0009). PFS was improved in patients with excess weight (7.25 months vs 4 months, HR 1.72, p = .01). The incidence of IrAEs was not different in patients with excess weight (54.5% vs 43.2%, p = .21). When high BMI and irAEs were combined, we observed a marked prognostic trend in ORR rate (87.5% vs 6.2%; OR 161.0, p < .00001), and in PFS (14 months vs 3 months; HR 5.89, p < .0001). Excess weight patients with advanced cancer that receive single-agent anti-PD-1 antibody therapy exhibit a significantly improved clinical outcome compared with normal BMI patients. This association was especially marked when BMI and irAEs were considered combined.
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Sarcopenic overweight is associated with early acute limiting toxicity of anti-PD1 checkpoint inhibitors in melanoma patients.
Heidelberger V, Goldwasser F, Kramkimel N, et al.
Invest New Drugs 2017;35(4):436–41.
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/m2 and 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.
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