Is it safe to directly upgrade from 11.2.1 to 11.5.1?

Generally speaking YES (based on my experience), but reading Release Notes is mandatory! What modules are you using? LTM GTM ...

I'm currently using LTM but in vCMP environment.

Absolutely. Great suggestion above re Release Notes. Biggest thing to be aware of is the change from HTTP Class to Local Traffic Policies. A few SOLs on askf5 in regards upgrading HTTP Class profiles/irule commands and events to new Local Traffic Policies.