Abstract 7044

Activity of ofatumumab, a novel CD20 mAb, and prior rituximab exposure in patients with fludarabine- and alemtuzumab-refractory or bulky fludarabine-refractory chronic lymphocytic leukemia

W.G. Wierda, T. Kipps, J. Mayer, et al

Methods: This pivotal, international study assessed efficacy by prior rituximab (Rituxan) exposure in 138 patients with chronic lymphocytic leukemia (CLL). The primary endpoint was overall response rate (ORR) over 24 weeks. Patients received 8 weekly infusions of ofatumumab followed by 4 monthly infusions (dose 1: 300 mg; doses 2–12: 2,000 mg).
Results: Among 59 double-refractory (DR) patients, ORR at the planned interim analysis was 58% (74% in the DR group and 62% in the bulky fludarabine-refractory [BFR] group). The secondary endpoint of median progression-free survival (PFS) was reported at 13.7 and 15.4 months in the DR and BFR groups, respectively. ORR and median PFS were similar among those with and without prior rituximab-treatment (59% in the DR group and 54% in the BFR group), and similar when comparing individual groups to the entire population. ORR and median PFS were also similar in patients refractory to fludarabine in combination with rituximab with or without cyclophosphamide.

Efficacy Outcomes by RTX Exposure

DR (n = 59)

BFR (n = 79)

Prior RTX

N

ORR (95% CI)

Median PFS (95% CI)

N

ORR (95% CI)

Median PFS (95% CI)

Any prior RTX*

35

54% (37%–71%)

5.5 mo (3.7–8.0 mo)

43

44% (29%–60%)

5.5 mo (3.8–6.4 mo)

FR†

18

50% (26%–74%)

5.5 mo (2.8–8.3 mo)

27

52% (32%–71%)

5.6 mo (2.5–7.4 mo)

FCR‡

16

50% (25%–75%)

4.6 mo (2.3–6.4 mo)

16

44% (20%–70%)

5.6 mo (2.1–6.6 mo)

No prior RTX

24

63% (41%–81%)

7.1 mo (4.8–8.7 mo)

36

50% (33%–67%)

6.4 mo (4.0–8.0 mo)

BFR = bulky fludarabine refractory; CI = confidence interval; DR = double-refractory; FCR = fludarabine, cyclophosphamide and RTX; FR = fludarabine plus RTX; ORR = overall response rate; PFS =progression-free survival; RTX = rituximab.

Conclusions: Treatment of CLL with the novel CD20 monoclonal antibody ofatumumab is effective regardless of double-refractory or bulky fludarabine-refractory disease and irrespective of prior treatment with rituximab.