Long-term Follow-up from A041202 Shows Continued Efficacy of Ibrutinib Regimens for Older Adults with CLL.

A041202 (NCT01886872) is a phase 3 study comparing bendamustine plus rituximab (BR) with ibrutinib and the combination of ibrutinib plus rituximab (IR) in previously untreated older patients with CLL. Initial results showed that ibrutinib-containing regimens had superior PFS and rituximab did not add additional benefit. Here we present an updated analysis. With median follow-up of 55 months, median PFS was 44 months (95% CI 38-54) for BR and not yet reached in either ibrutinib-containing arm. 48-month PFS estimates were 47%, 76% and 76% for BR, ibrutinib, and IR respectively. The benefit of ibrutinib regimens over CIT was consistent across subgroups of patients defined by TP53 abnormalities, del(11q), complex karyotype, and IGHV. No significant interaction effects were observed between treatment arm and del(11q), complex karyotype, or IGHV. However, a greater difference in PFS was observed among patients with TP53 abnormalities. There remains no difference in OS. Notable adverse events with ibrutinib include atrial fibrillation (afib) and hypertension. Afib was seen in 11 pts on BR (3%) and 67 pts on ibrutinib (18%). All grade hypertension was seen in 95 pts on BR (27%) and 263 pts on ibrutinib (55%). These data show that ibrutinib regimens prolong PFS over BR for older patients with treatment-naïve CLL. These benefits are seen across subgroups, including high risk groups. Strikingly, within the ibrutinib arms, there does not appear to be inferior PFS for patients with abnormalities in TP53, the highest risk feature seen in CLL. This differentiates ibrutinib from other treatment paradigms for treatment-naïve CLL.