Emavusertib (IRAK4i) + Ibrutinib Achieves 4/6 Deep Responses in MyD88-mutant R/R PCNSL, with CSF Levels Rising Two-fold at 200 mg BID

Emavusertib, an oral, brain-penetrant IRAK4 inhibitor, was paired with ibrutinib 560 mg QD in the phase 1/2 TakeAim‐Lymphoma trial (NCT03328078). Among seven patients with relapsed/refractory primary CNS-lymphoma who received cerebrospinal-fluid pharmacokinetic sampling, mean emavusertib CSF concentrations were 81 ng/mL at 100 mg BID and 176 ng/mL at 200 mg BID (2.2× increase; p = 0.02). Six of the seven harboured MyD88 mutations; four responded to the combination (three CR, one PR) with ongoing responses up to 18.9 months, despite prior BTK-inhibitor exposure. Historical ibrutinib monotherapy in PCNSL with MyD88 mutations yields ~67% ORR, 52% CR and a median PFS near 3 months, underscoring the combinatorial durability seen here.