The monoclonal antibody to cytotoxic T lymphocyte antigen 4, ipilimumab, in the treatment of melanoma

Figures & data

Figure 1 When an antigen (Ag) is presented in the context of the major histocompatibility complex (MHC) to the T cell receptor (TCR), binding of B7 with CD28 occurs which activates the T cell. Slightly later, the activated T cell stimulates CTLA4 which also binds to B7 to down-regulate the T cell. Ipilimumab inactivates the binding of CTLA4 with B7, allowing the T cell to remain activated.

Abbreviations: Ag, antigen; MHC, major histocompatibility complex; TCR, T cell receptor.

Table 1 Treatment outcome with diarrhea

Grade	Length of diarrhea	% episodes (from 5 studies)	Treatment	Outcome
1	≤5 days	46%	Symptomatically without immunosuppressive agents	87% resolution
1	>5 days	18%	Symptomatically with immunosuppressive agents	67% resolution
2	<3 days	12%	Symptomatically	Majority resolved
2	>3 days	10%	Symptomatically with immunosuppressive agents	Majority resolved
≥3	Any	13%	Symptomatically with immunosuppressive agents	>90% resolution within 2 weeks (median 1 week)

Table 2 Immunosuppressive guidelines

Grade	Description	Treatment	Outcome
1	Less than 4 stools/day	Start loperamide, 1 pill after each liquid stool Drink gatorade	Does not resolve after 48 hours, call clinic
2	Between 4–6 stools/day	Start loperamide, 1 pill after each liquid stool Drink gatorade	Does not resolve after 48 hours, call clinic
3	7 or more stools/day Up and going normally 7 or more stools/day Bedridden or weak	Start budesonide 1 pill/day and loperamide, 1 pill after each liquid stool Drink gatorade Take Budesonide 1 pill, and either go to clinic or ER and tell the ER doctor to call the oncology attending immediately	Does not resolve after 24 hours, call clinic

Table 3 Doses of immunosuppressive agents

Drug	Dose	Outcome
Budesonide	3 mg/day	If no benefit after 48 hours go to intravenous prednisone Order a colonoscopy to diagnose the colitis
Prednisone	Start with intravenous methylprednisolone 125 mg twice a day down to 60 mg daily within 1 week, then administer a 30 day tapering course of prednisone starting at 60 mg by mouth daily	If worsening go to aflibercept
Aflibercept	5 mg/kg intravenously