CTLA4 and hyperinsulinemic hypoglycemia, familial, 4: There was no increase in incidence of immune-mediated SAEs, consistent with the observation that LAG-3 deficiency alone does not result in autoimmunity in preclinical models.26 In contrast to combination checkpoint blockade with anti-CTLA-4 and anti-PD-1 agents, the immune-mediated toxicity of ieramilimab in combination with spartalizumab was comparable to that seen with spartalizumab alone.14 No new safety signals were identified compared with existing immune checkpoint inhibitor treatments.