Table 1.

Studies supporting the obesity paradox for cancer immunotherapy outcomes.

First author (Year)	Tumor type	Cohort size	Trial name or SOC	Obesity metric used	ICI used	Controlled prognostic factors	Outcomes
McQuade (34)	melanoma	213 males	retrospective analyses from 4 US and Australian centers	BMI: per WHO for NW, OVWT, OB.	anti-PD-1, anti-PD-L1, or anti-CTLA-4 + dacarbazine (chemotherapy)	age, AJCC & disease stage, LDH status, ECOG status	OB vs NW: males have improved PFS and OS
				UWT excluded
Donnelly (37)	melanoma	423	prospective NYU Interdisciplinary Melanoma Cooperative Group	BMI: per WHO standards for UW, NW, OVWT, OB	anti-PD-1, anti-CTLA-4, or combination	1st versus 2nd+ line therapy; age, gender, tumor stage, LDH, ECOG, # metastatic sites	OB and OVWT: 1st line ICI trended toward improved PFS and OS.
							OB and OVWT with combo Tx: improved PFS and trend toward improved OS
Khojandi (30)	melanoma	129	trial NCT00094653	BMI: OB vs OVWT+NW+UWT	anti-CTLA-4	sex	OB improved OS
Labadie (38)	RCC	90	Mix of trials and retrospective	BMI: per WHO standards for UW, NW, OVWT, OB	mixed anti-PD-1/PD-L1	primary resistance versus primary response to ICI	Primary response in 58%: improved PFS with increasing BMI and irAE occurrence
Sanchez (32)	RCC	129	MSK Observational Immunotherapy Cohort	BMI: per WHO standards for OB vs NW	mixed: anti-PD-1, anti-PD-L1, anti-PD-1+anti-CTLA-4, anti-PD-1+anti-PD-L1	age, sex, IMDC score	OB: trend toward improved OS (not sig.). Unadjusted analysis without IMDC risk score showed OB was beneficial.
Kichenadasse (35)	NSCLC	1434	clinical trials: NCT02008227, NCT01903993, NCT02031458, NCT01846416	BMI: As per WHO for NW, OVWT, OB.	anti-PD-L1	age, sex, race, ECOG, smoking status, tumor subtype, # tumor sites, PD-L1 expression, LDH, CRP, NLR	OB vs NW: improved OS; especially for PD-L1+ tumors; no change in PFS.
				UWT excluded
							OVWT vs NW: improved OS; no change in PFS;
Wang (25)	Mixed (lung 22.0%, melanoma 13.6%, ovarian 8%, other 52%)	250	NR	BMI: OB vs UWT+ NW+ OVWT	anti-PD-1 or anti-PD-L1	age, sex, ECOG status, line of treatment, cancer type	OB: improved OS and PFS
Cortellini (39)	Mixed (65% NSCLC, 18.7% melanoma, 13.8% RCC, 2.4% other	976	17 center retrospective study	BMI: OVWT+ OB vs NW+UW	anti-PD-1 or anti-PD-L1	primary tumor type, sex, age, ECOG, treatment line, # metastatic sites	High BMI (OVWT+OB): improved PFS.
							OB vs NW: improved OS but not PFS. OVWT vs NW: improved PFS and OS.
							NW/UW patients: 25.2% had irAEs; OVWT/OB patients had 55.6% irAEs
An meta-analysis (40)	Mixed (68.2% NSCLC; 18.5% melanoma, 10.2% RCC)	5279	Mix of trials and retrospective	BMI: NW+UWT vs OVWT+OB	anti-PD-1, anti-PD-L1, anti-CTLA-4	NR	High BMI (OVWT+OB): improved OS and PFS; no difference in irAEs

For studies based upon the use of BMI as the obesity defining metric, UWT, underweight (BMI<18.5 kg/m²); NW, normal weight (BMI 18.5-24.9 kg/m²); OVWT, overweight (BMI 25-29.9 kg/m²); OB, obesity (BMI > 30 kg/m²). Note that non-significant data trends are indicated as such; all other outcomes listed are significant as per the original report. AJCC, American Joint Committee on Staging; CRP, C reactive protein; ECOG, Eastern Cooperative Oncology Group performance status; ICI, immune checkpoint inhibitor; irAEs, immune-related adverse events; LDH, lactate dehydrogenase; NLR, neutrophil to lymphocyte ratio; not sig, not significant; NR, not reported; NSCLC, non-small cell lung carcinoma; OS, overall survival; PFS, progression-free survival; RCC, renal cell carcinoma; SOC, standard of care; Tx, treatment.