If FR or Thomson left I dont think they would be very difficult to replace.
I think it is a very big "IF" and for the forseeable future very unlikely, especially with the likes of Thomson.
Luton is in a very unusual situation for a large airport when it comes to the charter traffic front, with Thomson as the only charter carrier really flying from the airport.
(There might be the occasional weekly charter with other airline, but nothing significant.)
While the glory days of Britannia at the airport are way behind us and Luton will play second fiddle to the larger regional airports for Thomson, they will continue to fly from here for years to come. Especially while Thomson head office is down the road and airline has offices and hangars at the airport.
Is it still the airlines HQ?
Thomson's base at the airport is still larger than many other UK airports they fly from.
Their flights nearly always fly full, and have a loyal following from regular seasoned passengers who use the airport. I have also noticed prices from Luton on flights regularly command a premium to other airports Thomson fly from on the same dates, with higher supplements on the same package holiday.
Even Monarch who have had a significant presence at the airport for years, haven't offered a decent charter programme in ages, with Cosmos just selling seats on their scheduled services. For the last few years their only charter flight was to Zakinthos, while at the likes on LGW, BHX and MAN the scheduled and charter programmes have co-existed.
It would be a real coup for the airport to attract the likes of Thomas Cook Airlines, but with them recently expanding at Stansted - basing another aircraft there this year and long hauls from next year. I think this is unlikely.
I think it is more likely before Thomson ever leave Luton, they would close their Stansted base first, and focus north London operations from here.
With regards to Ryanair, I think the base is more vulnerable than Thomson... (But I am not in anyway saying it is under threat.) Having AENA now as the airport owners, and Ryanair having a significant bases at their airports in Spain, I suspect Luton will do everything within reason to keep them and might even try to tempt them into growing the base, in years to come. Especially when their is so many new aircraft on order and only limited places they can be deplyed!