WARNING: The following contains major spoilers for Boruto: Naruto Next Generations Chapter #50, by Masashi Kishimoto, Mikio Ikemoto and Ukyo Kodachi, available now in English from Viz Media.
The Boruto manga elevates Isshiki Ōtsutsuki above the likes of Naruto and Sasuke as he brings his war to the Land of Fire. A lot of it has to do with his alien origin and supreme abilities, but as he comes searching for Kawaki, Boruto proves to be quite adaptive, using his own Karma mark to teleport them all to a secret space-time dimension so there won't be collateral damage and a high number of innocent casualties.
Unfortunately, this hasn't slowed Isshiki down one bit which leads to a brutal brawl as he pushes the Konoha ninjas to the brink. They catch a lucky break when Boruto uncovers a shocking secret regarding Isshiki, but it almost comes at the cost of Sasuke's life.
Naruto and Sasuke try their best but they can't take Isshiki down now that he's fully taken over Jigen's body with his own Karma mark. Naruto's use of Kurama, the Nine Tails Fox, plus Sasuke using his ocular jutsu techniques just can't cut it and there's a critical moment where Sasuke's pummelled badly with the villain grabbing his iconic sword.
With Naruto down, Boruto realizes he's about to see his mentor be impaled and so he dives forward to shield Sasuke, hopefully catching him in time so they can teleport away. In that split second, Isshiki is faster, yet he hesitates when Boruto covers Sasuke. The kid snatches his next father-figure away and whisks the veteran away, immediately recognizing a flaw in Isshiki's game plan: the alien ninja cannot kill Boruto.
This explains why he wouldn't (or couldn't) harm him in previous skirmishes, but it also deepens the mystery behind Isshiki's powers and overall directives. Seeing as Boruto has a Karma mark and is a vessel for Momoshiki, fans are wondering if Ōtsutsuki clan members cannot harm each other's vessels. That would be tantamount to harming each other so hopefully we learn the rules of war internally with the aliens. There were hints that Isshiki possibly foughtwith his partner Kaguya when they came to Earth in a retcon to the original Naruto series, though, so this is all speculation.
Other theorists are wondering if Isshiki might not want to kill Boruto because he could be interested in appropriating the Karma mark as well. He could reform it to possibly place himself in Boruto, overwriting Momoshiki, or it could be he wants to experiment and either control Boruto or Momoshiki himself. Either way, Boruto knows he's now the ultimate trump card. If Naruto gives him access to the Nine Tails and Sasuke offers him the protective Susanoo chakra shield, Boruto might become the ultimate, unkillable shinobi that Isshiki can't defeat.