TY - JOUR
T1 - Targeting BTK with ibrutinib in relapsed or refractory mantle-cell lymphoma
AU - Wang, Michael L.
AU - Rule, Simon
AU - Martin, Peter
AU - Goy, Andre
AU - Auer, Rebecca
AU - Kahl Wojciech Jurczak, Brad S.
AU - Advani, Ranjana H.
AU - Romaguera, Jorge E.
AU - Williams, Michael E.
AU - Barrientos, Jacqueline C.
AU - Chmielowska, Ewa
AU - Radford, John
AU - Stilgenbauer, Stephan
AU - Dreyling, Martin
AU - Jedrzejczak, Wieslaw Wiktor
AU - Johnson, Peter
AU - Spurgeon, Stephen E.
AU - Li, Lei
AU - Zhang, Liang
AU - Newberry, Kate
AU - Ou, Zhishuo
AU - Cheng, Nancy
AU - Fang, Bingliang
AU - McGreivy, Jesse
AU - Clow, Fong
AU - Buggy, Joseph J.
AU - Chang, Betty Y.
AU - Beaupre, Darrin M.
AU - Kunkel, Lori A.
AU - Blum, Kristie A.
PY - 2013
Y1 - 2013
N2 - BACKGROUND: Bruton's tyrosine kinase (BTK) is a mediator of the B-cell-receptor signaling pathway implicated in the pathogenesis of B-cell cancers. In a phase 1 study, ibrutinib, a BTK inhibitor, showed antitumor activity in several types of non-Hodgkin's lymphoma, including mantle-cell lymphoma. METHODS: In this phase 2 study, we investigated oral ibrutinib, at a daily dose of 560 mg, in 111 patients with relapsed or refractory mantle-cell lymphoma. Patients were enrolled into two groups: those who had previously received at least 2 cycles of bortezomib therapy and those who had received less than 2 complete cycles of bortezomib or had received no prior bortezomib therapy. The primary end point was the overall response rate. Secondary end points were duration of response, progression-free survival, overall survival, and safety. RESULTS: The median age was 68 years, and 86% of patients had intermediate-risk or high-risk mantle-cell lymphoma according to clinical prognostic factors. Patients had received a median of three prior therapies. The most common treatment-related adverse events were mild or moderate diarrhea, fatigue, and nausea. Grade 3 or higher hematologic events were infrequent and included neutropenia (in 16% of patients), thrombocytopenia (in 11%), and anemia (in 10%). A response rate of 68% (75 patients) was observed, with a complete response rate of 21% and a partial response rate of 47%; prior treatment with bortezomib had no effect on the response rate. With an estimated median follow-up of 15.3 months, the estimated median response duration was 17.5 months (95% confidence interval [CI], 15.8 to not reached), the estimated median progressionfree survival was 13.9 months (95% CI, 7.0 to not reached), and the median overall survival was not reached. The estimated rate of overall survival was 58% at 18 months. CONCLUSIONS: Ibrutinib shows durable single-agent efficacy in relapsed or refractory mantle-cell lymphoma. (Funded by Pharmacyclics and others; ClinicalTrials.gov number, NCT01236391.) Copyright © 2013 Massachusetts Medical Society.
AB - BACKGROUND: Bruton's tyrosine kinase (BTK) is a mediator of the B-cell-receptor signaling pathway implicated in the pathogenesis of B-cell cancers. In a phase 1 study, ibrutinib, a BTK inhibitor, showed antitumor activity in several types of non-Hodgkin's lymphoma, including mantle-cell lymphoma. METHODS: In this phase 2 study, we investigated oral ibrutinib, at a daily dose of 560 mg, in 111 patients with relapsed or refractory mantle-cell lymphoma. Patients were enrolled into two groups: those who had previously received at least 2 cycles of bortezomib therapy and those who had received less than 2 complete cycles of bortezomib or had received no prior bortezomib therapy. The primary end point was the overall response rate. Secondary end points were duration of response, progression-free survival, overall survival, and safety. RESULTS: The median age was 68 years, and 86% of patients had intermediate-risk or high-risk mantle-cell lymphoma according to clinical prognostic factors. Patients had received a median of three prior therapies. The most common treatment-related adverse events were mild or moderate diarrhea, fatigue, and nausea. Grade 3 or higher hematologic events were infrequent and included neutropenia (in 16% of patients), thrombocytopenia (in 11%), and anemia (in 10%). A response rate of 68% (75 patients) was observed, with a complete response rate of 21% and a partial response rate of 47%; prior treatment with bortezomib had no effect on the response rate. With an estimated median follow-up of 15.3 months, the estimated median response duration was 17.5 months (95% confidence interval [CI], 15.8 to not reached), the estimated median progressionfree survival was 13.9 months (95% CI, 7.0 to not reached), and the median overall survival was not reached. The estimated rate of overall survival was 58% at 18 months. CONCLUSIONS: Ibrutinib shows durable single-agent efficacy in relapsed or refractory mantle-cell lymphoma. (Funded by Pharmacyclics and others; ClinicalTrials.gov number, NCT01236391.) Copyright © 2013 Massachusetts Medical Society.
U2 - 10.1056/NEJMoa1306220
DO - 10.1056/NEJMoa1306220
M3 - Article
C2 - 23782157
SN - 1533-4406
VL - 369
SP - 507
EP - 516
JO - New England Journal Of Medicine
JF - New England Journal Of Medicine
IS - 6
ER -
