SEP support Windows server 2012 R2

I am using SEPM 12.1.RU6 and most of our client servers are running SEP 12.1.2015.2015. To support Windows server 2012 R2, what client version we must use? Can the previous package of SEP 12.1.2015.2015 work on Windows server 2012 R2? Or I have to gernerate package of SEP 12.1.RU6 ?

Is there any problem for SEPM management if we have multipule SEP client version. Thanks