The purpose of the filibuster is not to force everyone to listen to you read the phone book - it's to delay the matter before the Senate. So it would still be "effective" if everyone left, because if they aren't there, they obviously aren't voting on whatever it is you didn't want them to vote on.
According to Article I, Section 5 of the Constitution:
a Majority of each shall constitute a Quorum to do Business; but a
smaller Number may adjourn from day to day, and may be authorized to
compel the Attendance of absent Members, in such Manner, and under
such Penalties as each House may provide.
According to Senate rules:
No Senator shall absent himself from the service of the Senate
Whenever upon such roll call it shall be ascertained that a quorum is not present, a majority of the Senators present may direct the
Sergeant at Arms to request, and, when necessary, to compel the
attendance of the absent Senators, which order shall be determined
without debate; and pending its execution, and until a quorum shall be
present, no debate nor motion, except to adjourn, or to recess
pursuant to a previous order entered by unanimous consent, shall be in
So, the members left present could actually force the absent members to return (although if the majority didn't want to be there, they could just vote to officially recess or adjourn.)
But it also seems that if a quorum is not present, the person speaking could simply note the absence of a quorum, and debate would no longer be in order until a quorum was again present. This would allow them to stop talking, which they'd probably be happy about if they'd already been talking for an extended period.