phocytic Lymphoma) (NCT01611090) was conducted in patients with previously treated CLL or SLL. Patients (n = 578) were randomized 1:1 to receive either IMBRUVICA 420 mg daily or placebo in combination with BR until disease progression, or unacceptable toxicity. All patients received BR for a maximum of six 28-day cycles. Bendamustine was dosed at 70 mg/m2 infused IV over 30 minutes on Cycle 1, Days 2 and 3, and on Cycles 2-6, Days 1 and 2 for up to 6 cycles. Rituximab was administered at a dose of 375 mg/m2 in the first cycle, Day 1, and 500 mg/m2 Cycles 2 through 6, Day 1.
The median age was 64 years (range, 31 to 86 years), 66% were male, and 91% were Caucasian. All patients had a baseline ECOG performance status of 0 or 1. The median time since diagnosis was 5.9 years and the median number of prior treatments was 2 (range, 1 to 11 treatments). At baseline, 56% of patients had at least one tumor ≥ 5 cm and 26% presented with del11q.
Efficacy results for HELIOS are shown in TABLE 19 and the Kaplan-Meier curves for PFS are shown in FIGURE 4.
Table 19: Efficacy Results in Patients with CLL/SLL in HELIOS
Endpoint IMBRUVICA + BR
N=289 Placebo + BR
N=289
a IRC eva luated, Twenty four subjects (8.3%) in the IMBRUVICA + BR arm and six subjects (2.1%) in the placebo + BR arm achieved complete response
BR = bendamustine and rituximab; CI = confidence interval; HR = hazard ratio
Progression Free Survivala
Number of events (%) 56 (19.4) 183 (63.3)
Median (95% CI), months Not reached 13.3 (11.3, 13.9)
HR (95% CI) 0.20 (0.15, 0.28)
Overall Response Ratea 82.7% 67.8%
Figure 4: Kaplan-Meier Curve of Progression-Free Survival (ITT Population) in Patients with CLL/SLL in HELIOS
Figure 4
Lymphocytosis
Upon initiation of IMBRUVICA, an increase in lymphocyte counts (i.e., ≥ 50% increase from baseline and above absolute lymphocyte count of 5,000/mcL) occurred in 66% of patients in the CLL studies. The onset of isolated lymphocytosis occurs during the first month of IMBRUVICA therapy and resolves by a median of 14 weeks (range, 0.1 to 104 weeks). When IMBRUVICA was administered with chemoimmunotherapy, lymphocytosis was 7% with IMBRUVICA + BR versus 6% with placebo + BR.
14.3 Waldenström's Macroglobulinemia
The safety and efficacy of IMBRUVICA in WM were eva luated in Study PCYC-1118E (referred to as Study 1118) (NCT01614821), an open-label, multi-center, single-arm trial of 63 previously treated patients. The median age was 63 years (range, 44 to 86 years), 76% were male, and 95% were Caucasian. All patients had a baseline ECOG performance status of 0 or 1. The median time since diagnosis was 74 months, and the median number of prior treatments was 2 (range, 1 to 11 treatments). At baseline, the median serum IgM value was 3.5 g/dL (range, 0.7 to 8.4 g/dL).
IMBRUVICA was administered orally at 420 mg once daily until disease progression or unacceptable toxicity. The responses were assessed by investigators and IRC using criteria adopted from the International Workshop of Waldenström's Macroglobulinemia. Responses, defined as partial response or better, per IRC are shown in TABLE 20.
Table 20: Overall Response Rate (ORR) and Duration of Response (DOR) Based on IRC Assessment in Patients with WM in Study 1118
Total (N=63)
CI = confidence interval; NR = not reached
Response rate (CR+VGPR+PR), (%) 61.9
95% CI (%) (48.8, 73.9)
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