The first phase 3 superiority readout for a non-covalent BTK inhibitor.
Fact-checked 16 June 2026
AgentPirtobrutinib (non-covalent BTKi)
ResistanceOvercomes C481S
EfficacyPFS HR 0.547
DepthMRD 10⁻⁶ 52.1% vs 35.0%
PositiveProbably yes
BRUIN CLL-322
NCT04965493 · LBA5001 · Davids · 639 patients
Pirtobrutinib + venetoclax-rituximab vs venetoclax-rituximab
Median 2 prior lines; about 80% had a prior covalent BTK inhibitor
PFS HR 0.547 (0.400 to 0.748), P=0.0001
Undetectable MRD at 10⁻⁶ of 52.1% vs 35.0% at end of treatment
Results to be published in the Lancet
Why it matters: The first phase 3 superiority readout for a non-covalent BTK inhibitor, with benefit even after covalent BTKi exposure and overcoming the C481S resistance mutation.
MRD is becoming the common language across haematology.BRUIN CLL-322 and the myeloma trials measured depth of response in the same terms.