The best dosage of nivolumab plus ipilimumab combination for melanoma brain metastases

Tawbi et al. (2021) have recently reported that nivolumab 1 mg/kg plus ipilimumab 3 mg/kg every 3 weeks for four doses (N1I3) provided durable survival for patients with active melanoma brain metastases without symptoms as first-line regimen. While we believe in the usefulness of the regimen proposed by Tawbi et al. (2021) we sought to investigate whether the nivolumab 3 mg/kg plus ipilimumab 1 mg/kg every 3 weeks for four doses (N3I1) regimen might lead to better safety profile. To compare the risk of adverse events caused by these two regimes, we have recently conducted a meta-analysis using the data of patients with both melanoma and the other malignancies. N1I3 regimen, compared to N3I1 regimen, more frequently induced any adverse events (N1I3, 96%; N3I1, 85%; P = 0.003), grade III or higher adverse events (N1I3, 64%; N3I1, 36%; P < 0.001; Fig. 1), and serious adverse events (N1I3, 61%; N3I1, 48%; P = 0.004). In terms of organ specific side effects, the N1I3 regimen also caused significantly more hepatic dysfunction, diarrhea, colitis, and pyrexia. We hope that there will be further discussion on the best dosage of the combination therapy.