In a nutshell, the main things (to name a few that get it done) that keep the P-38 out of other twins' reach are counter-rotating engines and fowler flaps, good aerodynamics (it feels really clean to me at least) and boosted ailerons. Those put together mean that the 38 can far outperform its competition deep inside departure envelope, and also be in a class of its own in roll rate at high speed and probably in terms of high speed retention.
The P-38's 4x50 and 20mm all stuck together at the tip of the nose are very lethal, but in a close fight they're probably nothing like 410's better packages (obviously excluding awkward heavyweight packages like BK5) which don't even need that fraction of a second connection to guarantee a fighter kill - 4 20mm or 2 30mm probably guarantee a kill on any kind of snapshot. So the 410's handling is going to be critical. If it's as flaky as the Mossie used to be, the 38 is really gonna have a field day with it and the only exception will be those rare times a 410 gets a solution.
Look at the chart on this post:
http://bbs.hitechcreations.com/smf/index.php/topic,261828.msg3342438.html#msg3342438The P-38 is already ~30mph faster at sea level with its curve growing positive and never looking back from there. No competition in that respect. The 410 better handle well enough for the defensive position it'll most likely/often be in, otherwise even those 50cal-like MK 103 cannons won't save it.