PFS was significantly increased in the ibrutinib group compared with those receiving ofatumumab (see figure 1A). The PFS at 6 months was 88% for ibrutinib vs 65% for ofatumumab. Of note, those with the poor prognosis 17p deletion had a 6 month PFS of 83% on ibrutinib, compared with 49% in the ofatumumab group. OS was also significantly increased in the ibrutinib group (see figure 1B), despite a protocol amendment that allowed crossover from ofatumumab to ibrutinib in the setting of progressive disease. At 12 months, OS was 90% in the ibrutinib group, compared with 81% in the ofatumumab allocated group.r
In a 3 year follow up of patients treated on the original Phase 1b/2 and extension studies of ibrutinib in CLL (PCYC-1102 and PCYC-1103), median PFS and OS were not reached. Amongst the treatment naïve patients (n=31), PFS was 96% and OS 97% at 30 months, whilst the relapsed/refractory CLL patients (n=101) had a PFS of 69% and OS of 79% at 30 months.r
43% of patients receiving ibrutinib achieved a partial remission (PR) compared with only 4% in the ofatumumab group. In addition, a further 20% of ibrutinib patients had a PR with lymphocytosis, giving an overall response rate of 63%.r Lymphocytosis in patients receiving ibrutinib is a well described phenomenon that does not represent progressive disease and does not affect patient prognosis.r In the RESONATE study, lymphocytosis resolved in 77% of patients during the follow up period.r
In the 3 year follow up study, 73% of the 132 patients experienced lymphocytosis. The lymphocyte count peaked at a median of 4 weeks (range 0.6-132 weeks) then declined at a rate dependent on the genetic characteristics of the CLL (slower rate of decline in lower risk disease). All cases were asymptomatic and resolved with continued ibrutinib therapy at a median time of 19 weeks (range 1-124).r
Figure 1: Progression free (A) and overall (B) survival in ibrutinib vs ofatumumab treated groups.
© New England Journal of Medicine 2014