Our data demonstrate that LU-102 has superior synergistic cytotoxic activity with ibrutinib on MM and MCL cells, compared to BTZ, most likely due to its synergistic inhibition of p-IκB and the canonical NF-κB pathway, and that the combination of ibrutinib and LU-102 can overcome BTZ and CFZ resistance in vitro. Here, NFKB1 is linked to mantle cell lymphoma.