In March 2018, Xiaojun Huangfrom Peking University People's Hospital, Beijing, China, and colleagues published the results of a randomized open-label phase III trial (NCT01973387)on ibrutinib versusrituximab for relapsed/refractory (R/R) patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) in Cancer Medicine .
Despite the global advances in therapies for CLL/SLL patients, treatment options remain limited in the Asia-Pacific region and especially for difficult-to-treat R/R patients. In China, R/R CLL/SLL patients that do not respond to traditional chemotherapy are limited to rituximab or lenalidomide/thalidomide containing regimens. The aim of this trial was to evaluate the efficacy and safety of ibrutinib versusrituximab for the treatment of R/R CLL/SLL. The primary endpoints of the study were investigator-assessed progression-free survival (PFS), while secondary endpoints included overall response rate (ORR), overall survival (OS), and safety.
Patient characteristics & study design
- Patients (N = 160) with CLL/SLL enrolled at 29 sites in China, Australia, Taiwan and Malaysia were included in this randomized open-label phase III trial (70.6% males; 85% Chinese)
- Median age (range): 66 (21–87) years
- A large proportion of patients had advanced-stage CLL with high-risk features (bulky disease, 43.8%; del11q, 21.3%; del17p, 22.5% and unmutated immunoglobulin heavy chain variable region [IGVH], 61.3%)
- Random patient assignment 2:1 for 420 mg once daily oral ibrutinib (n = 106) until disease progression (PD) or unacceptable toxicity
ORintravenous rituximab, up to 6 cycles (n = 54)
- Rituximab dosing cycles: 375 mg/m 2on Day 1 and 500 mg/m 2on Day 15 of cycle 1; 500 mg/m 2on Days 1 and 15 for cycle 2; and 500 mg/m 2on Day 1 of cycles 3–6.
- Ibrutinib vsrituximab
- Median treatment duration: 16.4 vs6 months
- ORR: 53.8% vs 7.4% ( P< 0.0001)
- Ibrutinib improved PFS (hazard ratio [HR] = 0.180, 95% confidence interval [CI] [0.105–0.308])
- Ibrutinib improved OS as compared to rituximab (HR = 0.446; 95% CI [0.221–0.900]; P= 0.0206), at a median follow-up of 17.8 months.
- Overall incidence of adverse events (AEs) was similar between ibrutinib and rituximab and was not exposure-adjusted
- Ibrutinib-related most common AEs: diarrhea and platelet count decrease
- Rituximab-related most common AEs: neutrophil count and platelet count decrease
- Grade ≥3 AEs were reported in 82.7% of ibrutinib-treated patients and 59.6% of rituximab-treatment patients
- Incidence of bleeding AEs was 28.8% in the ibrutinib arm and 3.8% in the rituximab arm
- Major haemorrhage events occurred in n = 3 (2.9%) patients in the ibrutinib arm and n = 1 (1.9%) in the rituximab arm
The results of this phase III clinical trial indicate the superiority of ibrutinib over rituximab for the treatment of R/R CLL/SLL patients in the Asia-Pacific region. With similarly acceptable safety profiles, ibrutinib improved PFS, ORR and OS, when compared to rituximab treatment. According to the authors, these results are consistent with other global studies, indicating that ibrutinib’s efficacy and safety over rituximab is comparable to the values observed for the general population.