nistered orally at 420 mg once daily until disease progression or unacceptable toxicity. The ORR and DOR were assessed using a modified version of the International Workshop on CLL Criteria by an Independent Review Committee. The ORR was 58.3% (95% CI: 43.2%, 72.4%), all partial responses. None of the patients achieved a complete response. The DOR ranged from 5.6 to 24.2+ months. The median DOR was not reached.
RESONATE
The RESONATE study (A Randomized, Multicenter, Open-label, Phase 3 Study of the Bruton’s Tyrosine Kinase (BTK) Inhibitor Ibrutinib versus Ofatumumab in Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma) (NCT01578707) was conducted in patients with previously treated CLL or SLL. Patients (n=391) were randomized 1:1 to receive either IMBRUVICA 420 mg daily until disease progression, or unacceptable toxicity or ofatumumab at an initial dose of 300 mg, followed one week later by a dose of 2000 mg weekly for 7 doses and then every 4 weeks for 4 additional doses. Fifty seven patients randomized to ofatumumab crossed over following progression to receive IMBRUVICA. The median age was 67 years (range, 30 to 88 years), 68% were male, and 90% were Caucasian. All patients had a baseline ECOG performance status of 0 or 1. The trial enrolled 373 patients with CLL and 18 patients with SLL. The median time since diagnosis was 91 months and the median number of prior treatments was 2 (range, 1 to 13 treatments). At baseline, 58% of patients had at least one tumor ≥ 5 cm. Thirty-two percent of patients had 17p deletion.
Efficacy results for RESONATE are shown in TABLE 16 and the Kaplan-Meier curves for PFS, assessed by an IRC according to IWCLL criteria, and OS are shown in FIGURES 1 and 2, respectively.
Table 16: Efficacy Results in Patients with CLL/SLL in RESONATE
Endpoint IMBRUVICA
N=195 Ofatumumab
N=196
a Median OS not reached for either arm
b IRC eva luated. All partial responses achieved; none of the patients achieved a complete response.
CI = confidence interval; HR = hazard ratio; NR = not reached
Progression Free Survivalb
Number of events (%) 35 (17.9) 111 (56.6)
Disease progression 26 93
Death events 9 18
Median (95% CI), months NR 8.1 (7.2, 8.3)
HR (95% CI) 0.22 (0.15, 0.32)
Overall Survivala
Number of deaths (%) 16 (8.2) 33 (16.8)
HR (95% CI) 0.43 (0.24, 0.79)
Overall Response Rateb 42.6% 4.1%
Figure 1: Kaplan-Meier Curve of Progression Free Survival (ITT Population) in Patients with CLL/SLL in RESONATE
Figure 1
Figure 2: Kaplan-Meier Curve of Overall Survival (ITT Population) in Patients with CLL/SLL in RESONATE
Figure 2
CLL/SLL with 17p deletion (del 17p CLL/SLL) in RESONATE
RESONATE included 127 patients with del 17p CLL/SLL. The median age was 67 years (range, 30 to 84 years), 62% were male, and 88% were Caucasian. All patients had a baseline ECOG performance status of 0 or 1. PFS and ORR were assessed by an IRC. Efficacy results for del 17p CLL/SLL are shown in TABLE 17.
Table 17: Efficacy Results in Patients with del 17p CLL/SLL in RESONATE
Endpoint IMBRUVICA
N=63 Ofatumumab
N=64
a IRC eva luated. All partial responses achieved; none of the patients achieved a complete response.
CI = confidence interval; HR = hazard ratio; NR = not reached
Progre |
