The approach is the same as in a game like Pendragon (where Arthur, Lancelot, Merlin, etc. are NPCs). Here’s the advice the forthcoming RQ Campaign book has:
We encourage you to include well-known Gloranthan characters and events in your campaign. Their presence adds to the players’ experience and lends authority and authenticity. However, their inclusion always threatens the worst. For instance, what if Gunda the Guilty is facing the adventurers in battle and happens to roll a 00, while the adventurer rolls a critical success. What should you do? Here are some suggestions:You can fudge: “Well, a blow like that would have killed any normal mortal twice over, but not the mighty Gunda!”You can invoke a deus ex machina: “Gunda reels, but a spectral armed woman rides down from the sky. Everyone make a Cult Lore lore – it is one of Humakt’s choosers of the dead! She kneels over Gunda to tell her that it is not yet time to join Death, and kisses her gently on the lips. Gunda wakes, slightly dazed.
”How about surprise: “Gunda’s body falls to the ground. When you move forward to loot the body, make a Homeland Lore roll – made it? You realize this isn’t Gunda! Someone is wearing her armor and carries her weapons, but it is definitely not her!”Or do nothing. Change history. “The terrible Gunda the Guilty, boon companion of Harrek the Berserk, is dead.” And we pity the killer – as Harrek the Berserk will stop at nothing to avenge her death.You can even resurrect the character! Some characters like Argrath, the Feathered Horse Queen, Sir Ethilrist, and Jar-eel have escaped the Place of the Dead before and can do it again, others might be resurrected by their followers or community. “Sometime after the battle, you hear that Harrek traveled into Hell to rescue Gunda the Guilty and fought Death himself to do so. Despite bringing her back to the world of the living, the White Bear has announced that he shall kill everyone involved in Gunda’s death, and that he intends not only to kill them, but their families, and even their neighbors!”Most characters are dispensable anyway. Only the death of one of the five main characters would extensively change the campaign plot. And even that is not inviolate – although it does create additional work for you as your campaign will go in a very different direction without much guidance or support from published materials.
Changing history requires some forethought, but nothing requires you to follow the campaign to its predestined end. You may decide to throw predestination to the wind, let any player-character become the Prince of Sartar, and maybe even allow someone else to marry the Feathered Horse Queen and become the King of Dragon Pass. In the end, this campaign is yours to decide what you make of it.