Long-Term Outcome of Treatment-Naïve and Relapsed/Refractory Patients with CLL and TP53 Aberrations Treated with Ibrutinib, with or without Rituximab

Introduction: Ibrutinib has remarkably improved outcomes for patients with chronic lymphocytic leukemia (CLL), including those with TP53 aberrations (17p deletion and/or mutated TP53). However, patients harboring TP53 aberrations treated with ibrutinib have inferior outcomes compared to CLL patients without TP53 alterations. For example, in the RESONATE trial (Ibr arm), the median progression free survival (PFS) of patients with relapsed/refractory (R/R) CLL and carrying TP53 alterations was 40.7 months, but the median PFS was not reached in patients without TP53 alterations (Byrd, Blood 2019). Nevertheless, treatment-naive patients with TP53 aberrations treated with ibrutinib had a 6-year PFS of 61%, indicating a long-term PFS benefit in the frontline setting (Ahn, NEJM 2020). Here, we report the long-term outcomes for patients with CLL and TP53 aberrations in first-line and relapsed settings, as part of a randomized phase 2 study that compared ibrutinib (Ibr) monotherapy versus ibrutinib plus rituximab (Ibr + R) (NCT02007044).