Open AccessIbrutinib versus rituximab in relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma: a randomized, open‐label phase 3 study
Author(s) -
Huang Xiaojun,
Qiu Lugui,
Jin Jie,
Zhou Daobin,
Chen Xiequn,
Hou Ming,
Hu Jianda,
Hu Yu,
Ke Xiaoyan,
Li Junmin,
Liang Yingmin,
Liu Ting,
Lv Yue,
Ren Hanyun,
Sun Aining,
Wang Jianmin,
Zhao Chunting,
Salman Mariya,
Sun Steven,
Howes Angela,
Wang Jingzhao,
Wu Peng,
Li Jianyong
Publication year - 2018
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.1337
Subject(s) - ibrutinib , medicine , rituximab , chronic lymphocytic leukemia , adverse effect , hazard ratio , clinical endpoint , progression free survival , gastroenterology , oncology , lymphoma , leukemia , confidence interval , randomized controlled trial , chemotherapy
In the Asia‐Pacific region, treatment options are limited for patients with relapsed/refractory chronic lymphocytic leukemia ( CLL )/small lymphocytic lymphoma ( SLL ). Rituximab is widely used in this setting when purine analog‐based therapies are not appropriate. We evaluated the efficacy and safety of ibrutinib compared with rituximab in a randomized, open‐label phase 3 study in predominantly Asian patients with relapsed/refractory CLL / SLL . Patients ( N = 160) were randomly assigned 2:1 to receive 420 mg ibrutinib ( n = 106) until disease progression ( PD ) or unacceptable toxicity or up to six cycles of rituximab ( n = 54). The primary endpoint was investigator‐assessed progression‐free survival ( PFS ); key secondary endpoints were overall response rate ( ORR ), overall survival ( OS ), and safety. Rituximab‐treated patients could crossover to receive ibrutinib after confirmed PD . At data cutoff, median treatment duration was 16.4 months for ibrutinib and 4.6 months for rituximab. Ibrutinib significantly improved PFS (hazard ratio [ HR ] = 0.180, 95% confidence interval [ CI ]: 0.105–0.308). ORR was significantly higher ( P < 0.0001) with ibrutinib (53.8%) than with rituximab (7.4%). At a median follow‐up of 17.8 months, ibrutinib improved OS compared with rituximab ( HR = 0.446; 95% CI : 0.221–0.900; P = 0.0206). Overall incidence of adverse events ( AE s) was similar between treatments and was not exposure‐adjusted. With ibrutinib, most common AE s were diarrhea and platelet count decreased; with rituximab, most common AE s were neutrophil count decreased and platelet count decreased. Grade ≥3 AE s were reported in 82.7% of ibrutinib‐treated patients and 59.6% of rituximab‐treated patients. Ibrutinib improved PFS , ORR , and OS compared with rituximab and displayed a manageable safety profile in Asian patients with relapsed/refractory CLL / SLL .