Table 1.

Immunotherapy Toxicity

Type of Immunotherapy	General Symptoms	Skin Toxicity	GI Toxicity	Hepatotoxicity	Endocrinopathy	Other Toxicities
Vaccines	Fevers, chills, lethargy	Maculopapular, vitiligo1	Rare diarrhea5	Rare5	None	Local reactions, back pain,8 rare hypotension5
Cytokines: IFN	Fevers, chills, and flu-like symptoms19	Maculopapular19	Nausea, diarrhea, and rare vomiting22	Elevated LFTs common23	Thyroiditis; often associated with benefit24	Congestive heart failure,19 anemia,26 thrombocytopenia,26 leukopenia,26 depression21
Cytokines: IL-2	Fevers, chills, and lethargy31	Petechial and macular31	Transient nausea, vomiting, and diarrhea31	Elevated LFTs and bilirubin common31	Thyroiditis; often associated with benefit36	Pulmonary edema,32 hypotension,32 azotemia,32 myocarditis,32 altered mental status31
Cell therapy: TILs	Fevers, chills, and fatigue43–45	Maculopapular43	Rare diarrhea43–45	Elevated LFTs rare43–45	Thyroiditis; often associated with benefit43–45	Prolonged lymphopenia, CMV infections43–45
Cell therapy: CAR	Fevers, chills, and lethargy	Maculopapular	Rare diarrhea	Elevated LFTs with CA-IX CAR56	None	Cytokine release with tachycardia, hypotension, oliguria; B-cell aplasia54; pulmonary edema55
Cell therapy: TCR	Fevers, chills, and lethargy47	Maculopapular,47 vitiligo 52	Colitis with CEA TCR53	Elevated LFTs rare47	None	Encephalopathy59 and carditis60 with MAGE-3 TCR
Checkpoint protein inhibition: CTLA-4	Fevers, chills, and lethargy62	Maculopapular62	Diarrhea and colitis with ulceration62	Elevated LFTs62	Hypophysitis, thyroiditis, and adrenal insufficiency62	Neuropathy, nephritis, Guillain-Barré, myasthenia gravis, sarcoid, and thrombocytopenia all rare62,63
Checkpoint protein inhibition: PD-1	Fevers, chills, and lethargy68–72	Maculopapular68–72	Diarrhea and colitis with ulceration: uncommon68–72	Elevated LFTs uncommon68–72	Hypophysitis, thyroiditis more common, adrenal insufficiency68–72	Pneumonitis not common; neuropathy, Guillain-Barré, myasthenia gravis, nephritis, all rare68–72
Checkpoint protein inhibition: PD-L1	Fevers, chills, and lethargy81,82	Maculopapular81,82	Diarrhea and colitis with ulceration: rare81,82	Elevated LFTs rare81,82	Hypophysitis, thyroiditis more common, adrenal insufficiency81,82	Pneumonitis rare; anemia rare81,82
Combination checkpoint protein inhibition	Fevers, chills, and lethargy100	Maculopapular100	Diarrhea and colitis with ulceration; pancreatic lab elevation common100	Elevated LFTs common100	Hypophysitis, thyroiditis more common, adrenal insufficiency100	Pneumonitis not common100; neuropathy, Guillain-Barré, myasthenia gravis, nephritis, all rare100

Abbreviations: CA-IX, carbonic anhydrase IX; CAR, chimeric antigen receptor; CEA, carcinoembryonic antigen; CMV, cytomegalovirus; IFN, interferon; IL-2, interleukin-2; LFTs, liver function tests; TCR, T-cell receptor; TILs, tumor-infiltrating lymphocytes.