@Strat2Die4 I don't think that is the problem. It occurs also if I just open the media player or just a browser with Youtube. And it's a gaming laptop with horrendous processing power ;-)
It happens when playing audio from any application. After a clean reboot, the problem is not there, but then after a few minutes it starts with -say- one glitch per minute, and then gradually it gets worse and worse until they come every few seconds and it becomes unworkable. It seems like some internal buffer is overflowing or something.
The problem does not occur if I stream audio to the headphones output or the internal speakers: only if I stream via USB to the POD HD500X.
I already upgraded/reinstalled the Line6 drivers and I also updates the laptop USB drivers as @TheRealZap suggested, but no success. My previous laptop was also an MSI, and never had any problems in the interface with the POD....