Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2025
Phase III Trial of Pirtobrutinib Versus Idelalisib/Rituximab or Bendamustine/Rituximab in Covalent Bruton Tyrosine Kinase Inhibitor-Pretreated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (BRUIN CLL-321).
СтатьяКлиническое исследование III фазыРандомизированное исследованиеМногоцентровое исследованиеСравнительное исследованиеПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Sharman Jeff P, Munir Talha, Grosicki Sebastian, Roeker Lindsey E, Burke John M, Chen Christine I, Grzasko Norbert, Follows George, Mátrai Zoltán, Sanna Alessandro, Qiu Lugui, Feng Ru, Hua Vu Minh, Jurczak Wojciech, Ritgen Matthias, Yi Shuhua, Bosch Francesc, Coombs Catherine C, Bao Katherine, Patel Vishalkumar, Liu Bin, Compte Livia, Guntur Ananya, Wang Denise Y, Hill Marisa, Leow Ching Ching, Ghia Paolo, Barr Paul M
Аннотация
PURPOSE: Pirtobrutinib, a noncovalent, Bruton tyrosine kinase inhibitor (BTKi), has shown clinical efficacy and a favorable safety profile. BRUIN CLL-321 was an open-label, randomized phase III study conducted exclusively in patients with R/R chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) previously treated with cBTKi, and compared pirtobrutinib with investigator's choice (IC) of idelalisib/rituximab (IdelaR) or bendamustine/rituximab (BR).
METHODS: Patients were randomly assigned 1:1 to receive pirtobrutinib (200 mg once daily) or IC of IdelaR or BR, and were stratified by previous use of venetoclax and del(17p). The primary end point was independent review committee-assessed progression-free survival (PFS). Secondary end points included time to next treatment or death (TTNT), overall survival (OS), and safety. The primary PFS end point was met at the time of the primary analysis (August 29, 2023), and updated results are reported from the final OS analysis (August 29, 2024).
RESULTS: A total of 238 patients were randomly assigned to receive pirtobrutinib (n = 119) or IC (n = 119; IdelaR [n = 82], BR [n = 37]). The PFS hazard ratio (HR) was 0.54 ([95% CI, 0.39 to 0.75]; P = .0002), with a median PFS of 14 months (95% CI, 11.2 to 16.6) in the pirtobrutinib group and 8.7 months (95% CI, 8.1 to 10.4) with IC. The unadjusted OS HR was 1.09 ([95% CI, 0.68 to 1.75]; P = .7202), and 18-month OS rate was 73.4% (95% CI, 63.9 to 80.7) in the pirtobrutinib group and 70.8% (95% CI, 60.9 to 78.7) with IC. Median TTNT was 24 months (95% CI, 17.8 to 29.7) with pirtobrutinib versus 10.9 months (95% CI, 8.7 to 12.5) with IC (HR, 0.37 [95% CI, 0.25 to 0.52]). At a median follow-up of 17.2 months, grade ≥3 treatment-emergent adverse events (AEs) were lower with pirtobrutinib (57.7%) than IC (73.4%). Treatment discontinuation due to AE occurred in 20 (17.2%) patients receiving pirtobrutinib and 38 (34.9%) patients receiving IC.
CONCLUSION: Pirtobrutinib improved PFS and TTNT, and demonstrated favorable tolerability, versus IdelaR/BR in exclusively cBTKi pretreated patients with CLL/SLL.
METHODS: Patients were randomly assigned 1:1 to receive pirtobrutinib (200 mg once daily) or IC of IdelaR or BR, and were stratified by previous use of venetoclax and del(17p). The primary end point was independent review committee-assessed progression-free survival (PFS). Secondary end points included time to next treatment or death (TTNT), overall survival (OS), and safety. The primary PFS end point was met at the time of the primary analysis (August 29, 2023), and updated results are reported from the final OS analysis (August 29, 2024).
RESULTS: A total of 238 patients were randomly assigned to receive pirtobrutinib (n = 119) or IC (n = 119; IdelaR [n = 82], BR [n = 37]). The PFS hazard ratio (HR) was 0.54 ([95% CI, 0.39 to 0.75]; P = .0002), with a median PFS of 14 months (95% CI, 11.2 to 16.6) in the pirtobrutinib group and 8.7 months (95% CI, 8.1 to 10.4) with IC. The unadjusted OS HR was 1.09 ([95% CI, 0.68 to 1.75]; P = .7202), and 18-month OS rate was 73.4% (95% CI, 63.9 to 80.7) in the pirtobrutinib group and 70.8% (95% CI, 60.9 to 78.7) with IC. Median TTNT was 24 months (95% CI, 17.8 to 29.7) with pirtobrutinib versus 10.9 months (95% CI, 8.7 to 12.5) with IC (HR, 0.37 [95% CI, 0.25 to 0.52]). At a median follow-up of 17.2 months, grade ≥3 treatment-emergent adverse events (AEs) were lower with pirtobrutinib (57.7%) than IC (73.4%). Treatment discontinuation due to AE occurred in 20 (17.2%) patients receiving pirtobrutinib and 38 (34.9%) patients receiving IC.
CONCLUSION: Pirtobrutinib improved PFS and TTNT, and demonstrated favorable tolerability, versus IdelaR/BR in exclusively cBTKi pretreated patients with CLL/SLL.
Предметные рубрики MeSH
HumansMaleFemaleAgedAntineoplastic Combined Chemotherapy ProtocolsLeukemia, Lymphocytic, Chronic, B-CellMiddle AgedBendamustine HydrochlorideRituximabQuinazolinonesPyrimidinesAgammaglobulinaemia Tyrosine KinaseProtein Kinase InhibitorsAged, 80 and overAdultProgression-Free SurvivalTyrosine Kinase InhibitorsPurinesPyrazoles