{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T17:54:43Z","timestamp":1790963683336,"version":"4.1.0"},"reference-count":0,"publisher":"American Society of Hematology","license":[{"start":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T00:00:00Z","timestamp":1790899200000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"abstract":"<jats:p>Primary central nervous system lymphoma (PCNSL) is an aggressive subtype of non-Hodgkin lymphoma with a poor prognosis, high rate of refractory or relapsed (R\/R) disease, and no established standard of care for R\/R PCNSL. This phase 2 study evaluated the efficacy and safety of tirabrutinib, a potent, highly selective, second-generation Bruton tyrosine kinase inhibitor, in patients with R\/R PCNSL in the US. In the open-label PROSPECT study, adults with R\/R PCNSL whose disease progressed on or after \u22651 high-dose methotrexate-based therapy received once-daily oral tirabrutinib 480 mg. The primary endpoint was overall response rate (ORR), and secondary endpoints included complete response (CR) rate, duration of response (DOR), and time to response (TTR), as assessed by independent review committee. Safety was assessed by frequency and severity of treatment-emergent adverse events (TEAEs). Among 48 enrolled patients, median follow-up was 11.5 months, ORR was 67% (95% confidence interval [CI], 52-80), and CR rate was 44% (95% CI, 29-59). Median DOR was 9.3 months (95% CI, 4.6-14.6), and median TTR was 1.0 month (range, 0.9-3.7). Treatment-related TEAEs occurred in 36 patients (75%), most commonly anemia (19%), maculopapular rash (17%), fatigue (15%), neutropenia (15%), lymphocytopenia (15%), pruritus (15%), and other rash (15%). Grade \u22653 treatment-related TEAEs occurred in 13 patients (27%), most commonly neutropenia (8%) and maculopapular rash (6%). One death (bronchopulmonary aspergillosis) was treatment related. In patients with R\/R PCNSL, once-daily oral tirabrutinib monotherapy resulted in rapid and durable responses and demonstrated a favorable safety profile. This trial was registered at www.clinicaltrials.gov as NCT04947319.<\/jats:p>","DOI":"10.1182\/blood.2026034926","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T18:58:40Z","timestamp":1790881120000},"update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":0,"title":["Efficacy and safety of tirabrutinib monotherapy for relapsed\/refractory primary CNS lymphoma: PROSPECT phase 2 trial"],"prefix":"10.1182","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7485-0441","authenticated-orcid":false,"given":"Christian","family":"Grommes","sequence":"first","affiliation":[{"name":"Memorial-Sloan Kettering Cancer Center, New York, New York, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lakshmi","family":"Nayak","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute, Boston, Massachusetts, United 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Huntsman Cancer Institute, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-5506-3301","authenticated-orcid":false,"given":"Dawit","family":"Aregawi","sequence":"additional","affiliation":[{"name":"Penn State Cancer Institute, Hershey, Pennsylvania, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley","family":"Sumrall","sequence":"additional","affiliation":[{"name":"Atrium Health Levine Cancer, Charlotte, North Carolina, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Omuro","sequence":"additional","affiliation":[{"name":"Yale School of Medicine, New Haven, CT, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1397-9927","authenticated-orcid":false,"given":"Fabio M.","family":"Iwamoto","sequence":"additional","affiliation":[{"name":"Columbia University Irving Medical Center, New 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BOSTON, Massachusetts, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4664-670X","authenticated-orcid":false,"given":"Lauren R.","family":"Schaff","sequence":"additional","affiliation":[{"name":"Memorial Sloan Kettering Cancer Center, New York, New York, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0456-5618","authenticated-orcid":false,"given":"Andrew","family":"Ip","sequence":"additional","affiliation":[{"name":"John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neel K.","family":"Gupta","sequence":"additional","affiliation":[{"name":"Stanford University, Stanford, California, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Drappatz","sequence":"additional","affiliation":[{"name":"UPMC Hillman Cancer Center, Pittsburgh, PA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vyshak A","family":"Venur","sequence":"additional","affiliation":[{"name":"Fred Hutch Cancer Center, University of Washington, Seattle, Washington, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine B.","family":"Peters","sequence":"additional","affiliation":[{"name":"Duke University Medical Center, Durham, North Carolina, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ka-Wai G","family":"Ho","sequence":"additional","affiliation":[{"name":"Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan","family":"Merrell","sequence":"additional","affiliation":[{"name":"Vanderbilt University Medical Center, Nashville, Tennessee, United 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