Table 2.

Comparison of subject patient with other published cases of cytokine release syndrome with MEKi/BRAFi

Characteristic	Subject patient	Case 1	Case 2A	Case 2B
Age (years)	58	47	48	48
Sex	Male	Male	Female	Female
Melanoma stage	IV	IV	IV	IV
Previous Treatment	Interferon, anti–PD‐1, MEKi/BRAFi	anti–PD‐1	anti–PD‐1, T‐VEC, anti‐LAG3	anti–PD‐1, T‐VEC, anti–PD‐1 again, anti‐LAG3, MEKi/BRAFi
MEKi/BRAFi	Cobimetinib/ Vemurafenib	Cobimetinib/ Vemurafenib	Trametinib/ Dabrafenib	Cobimetinib/ Vemurafenib
Time to CRS onseta	11 days	21 days	10 days	10 days
Fever	Yes	Yes	Yes	Yes
Hypotension	Yes	Yes	No	No
Cardiac	SVT, atrial fibrillation	Tachycardia, ventricular extrasystoles	Tachycardia	Tachycardia
Dermatologic	Purpura, blisters/bullae, Mucositis	Diffuse maculopapular	Generalized macular rash, erosive mucositis	Blisters/bullae, erosive stomatitis
Renal Insufficiency	Yes	Yes	No	No
Neurologic	Confusion	No	No	No
Gastrointestinal	Nausea, vomiting, diarrhea	No	No	No
Transaminitis	Yes	Yes	No	No
Cytopenias	Anemia, thrombocytopenia	Unknown	Leukopenia	Unknown
↑ inflammatory markers	Ferritin, CRP	CRP	Unknown	Unknown
↑Cytokines	IL‐1, IL‐2, IL‐4, IL‐5, IL‐6, IL‐8, IL‐10, IL‐13, IFN‐γ, TNF‐α	IL‐6, IFN‐γ, TNF‐α	IL‐6, IFN‐γ, TNF‐α	IL‐6, IFN‐γ
Treatment	Systemic CS, TCZ 400 mg × 2 doses	Local and systemic CS	Systemic CS	Systemic CS, TCZ 400 mg
Outcome	Discharged home	Developed tolerance to MEKi/BRAFi	Switched to cobimetinib/vemurafeni, had relapse of CRS (Case 2B)	Dramatic improvement following TCZ

^aTime to CRS following MEKi/BRAFi treatment.

Abbreviations: BRAFi, BRAF inhibitor; CRP, C‐reactive protein; CRS, cytokine release syndrome; CS, corticosteroids; IFN, interferon; IL, interleukin; LAG3, lymphocyte activation gene 3; MEKi, MEK inhibitor; PD‐1, programmed cell death protein 1; SVT, supraventricular tachycardia; TNF, tumor necrosis factor; T‐VEC, talimogene laherparepvec, TCZ, tocilizumab.