Aerosmith had two tours without Joe Perry and one album and one tour without either original guitarist. They reformed in 1984 and since then some members have missed tours for medical reasons but those hiatuses were understood to be temporary at the time. A couple years ago the drummer, Joey Kramer, sued because everyone else thought he needed to take a break because of his health and he didn't want to miss concerts, but they've since made up and as far as I can tell this really was a case of "I'm still sober enough to drive!" bullshit.
When Mitchell died I thought that the Jimi Hendrix Experience was the first major band to have a lineup lose all its members. Since then I know of two more:
- The original Ramones lineup are all dead. They recorded the first three albums. The former members who were not part of that lineup are all still alive.
- The Motorhead lineup who recorded the albums Motorhead-Iron Fist (this run includes Overkill and Ace of Spades) are all dead. This is usually considered the "classic" lineup and it's the first one to release recordings, but it is not the earliest lineup to have recordings that were released commercially. Because On Parole was recorded in 1976 and released in 1979.
Motorhead has a bunch of other dead members as well but of the different lineups they've had only the one is entirely dead.
Who are the bands with most dead former members?
Hawkwind has 10
Lynyrd Skynyrd has 10
The Allman Brothers have 8