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Table 2 Hazard ratios for the association of BMI with OS and PFS (along with interactions) and odds ratios for the association of BMI with durable clinical benefit among patients treated with anti-PD-1 based checkpoint inhibition

From: Complex inter-relationship of body mass index, gender and serum creatinine on survival: exploring the obesity paradox in melanoma patients treated with checkpoint inhibition

Outcome (N = 136)b

Effect Estimate

Overall Survival (OS)

Unadjusted Hazard Ratio (95% CI)

p-value

Adjusted Hazard Ratioa (95% CI)

p-value

Overweight/Class-I Obese vs. Normal Weight (reference)

0.41 (0.24–0.72)

0.002

0.26 (0.1–0.71)

0.008

Class-II/III Obese vs. Normal Weight

0.88 (0.41–1.91)

0.756

0.42 (0.1–1.77)

0.238

Interaction Modelc 1 (OS)

 Interaction of BMI (Overweight/Class-I vs. normal weight) with gender (males vs. females)

–

–

0.19 (0.04–0.95)

0.044

Interaction Model 1 (OS)

 Overweight/Class-I Obese (vs. normal weight) HR in females

–

–

0.56 (0.16–1.89)

0.346

Interaction Model 1 (OS)

 Overweight/Class-I Obese (vs. normal weight) HR in males

–

–

0.11 (0.03–0.4)

0.001

Interaction Model 2 (OS)

 Interaction of BMI (Overweight/Class-I vs. normal weight) with serum creatinine (> = 0.9 mg/dL vs. < 0.9 mg/dL)c

–

–

0.11 (0.02–0.7)

0.020

Interaction Model 2 (OS)

 Overweight/Class-I Obese (vs. normal weight) HR in patients with serum creatinine < 0.9 mg/dL

–

–

0.43 (0.15–1.24)

0.119

Interaction Model 2 (OS)

 Overweight/Class-I Obese (vs. normal weight) HR in patients with serum creatinine > = 0.9 mg/dL

–

–

0.045 (0.08–0.262)

0.001

Progression Free Survival (PFS)

 Overweight/Class-I Obese vs. Normal Weight (reference)

0.5 (0.31–0.81)

0.005

0.43 (0.19–0.95)

0.038

Class-II/III Obesity vs. Normal Weight

1.03 (0.53–2)

0.932

1 (0.34–2.94)

0.991

Interaction Model 1 (PFS)

 Interaction of BMI (overweight/Class-I vs. normal weight) with gender (males vs. females)

–

–

0.29 (0.07–1.18)

0.084

Interaction Model 1 (PFS)

 Overweight/Class-I Obese (vs. normal weight) HR in females

–

–

0.80 (0.27–2.41)

0.695

Interaction Model 1 (PFS)

 Overweight/Class-I Obese (vs. normal weight) HR in males

–

–

0.23 (0.08–0.66)

0.006

Interaction Model 2 (PFS)

 Interaction of BMI (overweight/Class-I vs. normal weight) with serum creatinine (> = 0.9 mg/dL vs. < 0.9 mg/dL)

–

–

0.17 (0.04–0.77)

0.021

Interaction Model 2 (PFS)

 Overweight/Class-I Obese (vs. normal weight) HR in patients with serum creatinine < 0.9 mg/dL

–

–

0.71 (0.29–1.77)

0.464

Interaction Model 2 (PFS)

 Overweight/Class-I Obese (vs. normal weight) HR in patients with serum creatinine > = 0.9 mg/dL

–

–

0.12 (0.03–0.45)

0.002

Durable Clinical Benefit (N = 132)b

Unadjusted Odds Ratio (95% CI)

p-value

Adjusted Odds Ratiod (95% CI)

p-value

Overweight/Class-I Obese vs. Normal Weight (reference)

2.76 (1.18–6.46)

0.020

11.4 (1.65–78.6)

0.013

Class-II/III Obesity vs. Normal Weight

0.91 (0.23–3.54)

0.891

3.3 (0.22–50.5)

0.391

Interaction Model 1 (DCB)

 Interaction of BMI (overweight/Class-I vs. normal weight) with gender (males vs. females)

–

–

10.39 (0.17–634.68)

0.265

Interaction Model 1 (DCB)

 Overweight/Class-I Obese (vs. normal weight) in females

–

–

2.91 (0.16–54.05)

0.473

Interaction Model 1 (DCB)

 Overweight/Class-I Obese (vs. normal weight) in males

–

–

30.27 (2.01–455.72)

0.014

Interaction Model 2 (DCB)

 Interaction of BMI (overweight/Class-I vs. normal weight) with creatinine (> = 0.9 mg/dL vs. < 0.9 mg/dL)

–

–

2.82 (0.03–229.67)

0.644

Interaction Model 2 (DCB)

 Overweight/Class-I Obese (vs. normal weight) HR in patients with serum creatinine < 0.9 mg/dL

–

–

8.03 (0.85–76.27)

0.070

Interaction Model 2 (DCB)

 Main effect (Serum Creatinine > = 0.9 mg/dL): Overweight/Class-I Obese (vs. normal weight) HR in patients with serum creatinine > = 0.9 mg/dL

–

–

22.66 (0.51–1013.5)

0.108

  1. a Adjusted for the following covariates: age (<=45, > 45–75 and > 75 years), gender, serum creatinine (< 0.9 and > = 0.9 mg/dL), treatment (monotherapy/combination), current drinker (vs. non-current/never-drinker), smoking history (ever vs. never), KPS (<=70 and > 70), LDH (<=231 vs. > 231 U/L), stage at baseline, Charlson’s score (< 10 vs. > = 10), hemoglobin (< 11.5 vs. > = 11.5 g/dL), ANC (<=8 and > 8 K/uL), ALC (< 3 and > =3 K/uL), albumin (< 3.5 g/dL), autoimmune disease, diabetes, CV disease, CKD, BRAF mutation, NRAS mutation, hypertension, hyperlipidemia, comedications (anti-platelet agents, statins, metformin, ACE/ARB inhibitors), prior treatments (immunotherapy/CTLA-4, radiation, chemotherapy and targeted therapy), fasting glucose (<=110 vs. > 110 mg/dL), type of melanoma,; N = 127 after excluding three patients who were underweight, 8 patients with missing LDH values and 1 patient whose KPS could not assessed (missing)
  2. b Three underweight patients were excluded
  3. c Interactions were studied in separate models along with main effects and adjusted for the same covariates as the main models
  4. d Adjusted for the same covariates listed for OS and PFS (except KPS which was included as a continuous variable); N = 123 (excluding 3 underweight patients; DCB was not assessable/available for 4 patients; patients with missing data for LDH, KPS were not included for the adjusted analysis)
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