if fucking VtM 5e didn't come out in the meantime and fucked up the VtM universe for good.
Wasn't VtmB already based on older lore when it came out anyway? I never read anything about VtM outside the games (VtmR and VtmB, not the newer games that i also haven't played) but i remember reading something like that. They could have just ignored 5e.
Also while the main story itself is self-contained, there are a few unfinished threads that could be used - like Maximilian Strauss' plans or whatever that is heavily hinted in the first game but never actually seem to happen. After VtmB there is a power vacuum in Camarilla's side that he would try to take advantage of, in a still unstable playfield - it isn't like Camarilla vampires would just pack and leave.
Of course that was written ~17 years ago and it is likely there are books or whatever describing what happened after the game that would make any sequel that tried to use those threads hard. But as i wrote i don't know about that, i just judge from the game itself and i do think there are things that could be expanded just based on it.