I don't think ToT is gonna happen--the situation is far too dire for the Lascaris cousins to make a play, and Alexandros Drakos has made his bed when it comes to the purple. However, D3 dying would be still quite bad for the Romans. Odesseus is too inexperienced, and he needs to learn his ropes. A couple of millitary blunders on the way (not quite on the scale of Basil II @ Trajan's gates, that can't happen with the current Roman army) are quite likely. These wont lead to major reversals in all likelihood, but prevent the Romans from fully capitalizing on their gains on the non Italy fronts.
O is also quite a bit away from the City, and there should be some chaos there if it becomes clear D3 was murdered (wrt spies, or enemies in general in the White Palace). A purge is possible, and the Empire will be acting like a headless chicken for a bit (even if D3's wife intervenes to steady the ship), putting the war effort on autopilot. This might be the closest Rome's enemies get to a respite. I still think they will be defeated, and in many cases defeated badly. But this might be the breathing room they need to regroup and fight for another two years.
The post war fate of D3's reforms is also interesting to consider, since idk what O thinks of them. His inclinations appear to be rather more millitary. Great, if D3 builds a sufficiently firm modern state to support it. Not so great if the foundation is not fully prepared.
Granted, I need to re-read many of the recent posts again before shooting my mouth off too much, but D3's health is the biggest challenge facing the Romans at the moment, with all the B444 foreshadowing.