Hello Mike,
4.2.1 gives ISSU infrastructure and supports 4.2.1 ISSUs SMUs only:
"For Cisco IOS XR Release 4.2.1, only Software Maintenance Upgrades (SMUs) that are identified and tagged as ISSU SMUs can be activated using ISSU."
http://www.cisco.com/en/US/docs/routers/asr9000/software/asr9k_r4.2/general/release/notes/reln_a9k_421.html#concept_3D4B5AA05D2340039E94917F84ACA856
For the future updates, even if a current version supports ISSU, that is not given ISSU would be possible for some new SW releases. For example ISSU upgrade won’t work if there would be a kernel change, or mandatory FPD upgrade or a major architecture change…
Regards,
/A