Table 1.

Summary of immunotherapy trials for cancer patients with bone metastasis

Immunotherapy	Study type	Treatment	Cancer	Outcome	Adverse events	Metastatic sites	PMID
Adoptive immunotherapies	Clinical Trial (Phase Unspecified, 1987, USA)	LAK	RCC	5 Bone metastatic patients: 2/5 had PR [Patient 1: < 6 months and Patient 2: no recurrence within 6 months]	Malaise, fever, renal failure	Bone, lung, brain, skin, liver, subcutaneous tissue, inferior vena cava	PMID: 2845776
Adoptive immunotherapies	Clinical Trial (Phase Unspecified, 1994, Japan)	LAK	RCC	2 Bone metastatic patients: 2/2 had PR [patient 1: < 10 months and patient 2: < 28 months]	Hypotension, heart failure, artery occlusion	Bone, muscle, brain, liver, lung, pleura, peritoneum	PMID: 7645136
Adoptive immunotherapies	Clinical Trial (Phase I, 1995, Japan)	LAK + IFN-#x3B1;	RCC	PD	Fever, anemia, gastric ulcers	Bone, lung, brain	PMID: 7609359
Adoptive immunotherapies	Case Report (2006, Japan)	Autologous T cell	BCa	CEA reduction, bone pain relief	NA	Bone	PMID: 16786141
Adoptive immunotherapies	Clinical Trial (Phase I, 2003, USA)	Autologous T cell	RCC	2 Bone metastatic patients: 2/2 had PR	Influenza-like symptoms	Bone, lung, brain, liver	PMID: 14506142
Adoptive immunotherapies	Clinical Trial (Phase III, 2006, USA)	Sipuleucel-T	CRPC	Extend median survival [25.9 months vs. placebo 21.4 months]	Anorexia, anxiety, depression, flank pain, hydronephrosis	Bone	PMID: 16809734
Adoptive immunotherapies	Clinical Trial (Phase III, 2010, USA)	Sipuleucel-T	CRPC	Extend median survival [25.8 months vs. placebo 21.7 months]	Anorexia, anxiety, depression, flank pain, hydronephrosis	Bone	PMID: 20818862
Adoptive immunotherapies	Clinical Trial (Phase III, 2015, USA)	Sipuleucel-T salvage	CRPC	Extend median survival [20.0 months vs. historical controls 9.8 months]	Chills, nausea, fever	Bone	PMID: 25943532
Adoptive immunotherapies	Clinical Trial (Phase I, 1988, USA)	TIL	Melanoma	CR or PR [10 patients without bone metastasis] and PR [1 patient with bone metastasis: 4 months]	Chills, nausea, vomiting, diarrhea	Bone, lung, brain, subcutaneous tissue, spleen	PMID: 3264384
Adoptive immunotherapies	Clinical Trial (Phase Unspecified, 1994, China)	TIL	Lung cancer, BCa, Gastric cancer	Extend median survival [183 days vs. standard of care therapy 82.3 days]	NA	Bone, lung, brain, liver	PMID: 7956700
Cytokine-based immunotherapy	Clinical Trial (Phase Unspecified, 2006, USA)	Famotidine + IL-2	Kidney cancer	6 Bone metastatic patients: 1/6 had CR [14 months] and 2/6 had PR [Patient 1: 3 months, Patient 2: 7 months]	Hypertension, elevated creatinine, pulmonary edema	Bone, lung, liver	PMID: 17105423
Cytokine-based immunotherapy	Clinical Trial (Phase III, 2008, USA)	IFN-α	RCC	Did not improve OS compared to Sunitinib	Fatigue, anemia, lymphopenia, nausea	Bone, lung, liver	PMID: 19487381
Immune checkpoint blockade	Retrospective Study (2020, China)	anti-PD-1 + antiangiogenic agent	NSCLC	ORR 19.3%	Proteinuria, Hypotension, Fatigue	Bone, liver, brain, adrenal gland	PMID: 33039958
Immune checkpoint blockade	Clinical Trial (Phase III, 2017, USA, France, Italy, Spain, Australia, Denmark, Finland, UK, Germany, Japan)	anti-PD-1	RCC	Extend median survival [18.5 months vs. chemotherapy 13.8 months]	Adverse events incidence reduced compared to chemotherapy	Bone, lung, liver	PMID: 28262413
Immune checkpoint blockade	Clinical Trial (Phase III, 2017, USA, Portland, France, Australia, Canada, Poland, Spain, Germany, Brazil, Mexico, Denmark, the Netherlands)	anti-CTLA-4	CRPC	Increased median PFS by 1.8 months compared to placebo	Diarrhea, rash, pruritus	Bone	PMID: 28034081

LAK lymphokine-activated killer cell therapy, TIL tumor-infiltrating lymphocytes therapy, RCC advanced renal cell carcinoma, BCa breast cancer, CRPC castration-resistant prostate cancer, NSCLC non-small cell lung cancer, CR complete response, PR partial response, PD progressed disease; OS overall survival, PFS progression-free survival, ORR objective response rate