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We know combo nivolumab + ipilimumab gives big results in melanoma, but it also gives big toxicity. Oncologists at Memorial Sloan Kettering observed 64 patients being treated on label with nivo + ipi for advanced melanoma to see how people in the real world fare with the side effects. Not good, we’re afraid. Three-quarters required steroids, half ended up in the emergency department, and one-third were hospitalized--all due to adverses events. In all, over 6 in 10 were not able to complete the recommended 4 cycles of therapy. The good news? There remain a lot of unexplored approaches to increasing the therapeutic window. First, the nivo:ipi dosing ratio (1:3) for melanoma may be reversed, as in other trials, to lower toxicity while maintaining response rates. Second, patients may not require the full 4 cycles to gain a benefit. TBL: Make no mistake, combo immunotherapy is tough to get through with most people having to stop early, but creative approaches may make it a little easier.