Tirabrutinib (ONO/GS-4059; Ono Pharmaceutical) is a newly developed drug that 
selectively and irreversibly inhibits Bruton's tyrosine kinase (BTK) and has 
been approved in Japan for treating relapsed/refractory primary central nervous 
system lymphoma (PCNSL). However, its therapeutic effect is yet to be verified 
at the pathological level in human patients. A 64-year-old patient with 
recurrent PCNSL enrolled in the phase I/II clinical trial of tirabrutinib, a 
second-generation BTK inhibitor designed for treating relapsed/refractory PCNSL. 
The left cerebellum lesions on magnetic resonance imaging disappeared one month 
after tirabrutinib treatment. The patient died because of suspected pneumocystis 
pneumonia and acute exacerbation of interstitial pneumonia 43 days after 
starting tirabrutinib. An autopsy confirmed no viable tumor cells in the entire 
brain, including the left cerebellum lesion, confirming complete obliteration of 
tumor cells by tirabrutinib. This letter pathologically confirms the effect of 
tirabrutinib on relapsed/refractory PCNSL for the first time in humans.Trial 
registration: JapicCTI-173646. Registered 14 July 2017, 
https://www.clinicaltrials.jp/cti-user/trial/ShowDirect.jsp?japicId=JapicCTI-173646.