- Ideal combinations should have complementary-not overlapping- mechanisms of immune activation to maximize benefit and minimize toxicity.
- Ipilimumab + nivolumab is clearly superior to ipilimumab alone, but the superiority of the combination compared with nivolumab alone is not clearly established. The risk of toxicity is significantly higher with combination therapy. We favor using ipilimumab + nivolumab in patients with multiple brain metastases who are not candidates for stereotactic radiosurgery, patients with mucosal melanoma, and those patients who are well enough.
- At this time, there are insufficient data to recommend the combination of checkpoint inhibitors + BRAF/MEK inhibition.
- While there is not clear evidence for improved efficacy with radiation therapy + checkpoint blockade, data suggest that the combination is safe, so concurrent treatment is reasonable to pursue when both modalities are independently indicated.