How to make an initialism out of a word/phrase with a number?
It's perfectly acceptable to use a 'numeronym'
A numeronym is a word where a number is used to form an abbreviation, such as K9 for canine, or W3 for World Wide Web etc.
https://en.wikipedia.org/wiki/Numeronym
Your reference of Rainbow 6 Siege as R6S is a perfectly acceptable numeronym.