Abstract
Patients with solid tumors and a higher body mass index (BMI) experience improved survival after receiving anti-PD1 antibodies. The predictive role of BMI in Hodgkin Lymphoma (HL), the most sensitive malignancy to PD1-blockade, remains unclear. We analyzed the association between BMI and survival outcomes in patients treated with the anti-PD-1 antibody nivolumab within the CheckMate 205 study. Patients with a lower BMI (<24.03 kg/m(2)) had a longer progression-free survival (PFS) (46.4% at three years) than those with a higher BMI (≥24.03 kg/m(2);19.6%; p = 0.03). Combining the BMI cutoff with serum creatinine (sCr) levels generated a variable (BMCI) stratifying patients into distinct PFS risk groups. Patients with a BMCI(high) (BMI ≥24.03 kg/m(2)/sCr <0.7 mg/dL) displayed a threefold increased PFS risk (95% CI,1.6-5.7; p < 0.001) than those with a BMCI(low) (BMI <24.03 kg/m(2)/sCr ≥0.7 mg/dL). In a separate analysis of pretreated patients, those with a BMCI(high) had a PFS risk 3.5-fold higher (95% CI,1.9-6.6; p < 0.001) than patients with a BMCI(low). The BMCI maintained its independent significance in a multivariable model including attenuating factors and predictive biomarkers. HL patients with reduced BMI but preserved lean body mass (BMCI(low)) exhibit a more favorable response to nivolumab. Results highlight an unexpected side of the 'obesity paradox' in HL.