OUTCOMES OF PATIENTS POST IBRUTINIB TREATMENT FOR RELAPSED/REFRACTORY CLL: A UK AND IRELAND ANALYSIS

Abstract

Introduction: Following discontinuation of ibrutinib, the outcome for many patients remains poor. This analysis was undertaken to gain a better understanding of how these challenging patients have been managed in the UK / Ireland. Methods: Data were collected on ibrutinib patients registered with the UK CLL Forum who had discontinued ibrutinib for any reason. Results: of the original 315 study patients, 140 have now stopped taking ibrutinib and 103 have died (median overall survival (mOS) 72 days from stopping (range: 0-919)). Patients stopped ibrutinib due to one of 6 broad reasons: 1. Adverse event (AE) - infection (n = 21; 15%) 2. AE - other (n = 41; 29%) 3. Second primary malignancy (n = 13; 9%) 4. Progressive Disease-CLL (PD CLL) (n = 25; 18%) 5. Progressive Disease-Richter's transformation (PDRT) (n = 28; 20%) 6. Other (predominantly no data given) (n = 12; 9%) Patients who stopped ibrutinib due to a non-infectious AE had the best survivals with 17/41 (41%) still alive. (mOS: 245 days (0-919)). The poorest survivals were seen for patients with PDRT where only 3 patients from 28 are still alive (Figure 1A). The rate of discontinuation of ibrutinib has reduced over time with 26.3% stopping in the first year, 16.8% (12.5-22.4)) in the second year and 11% beyond the second year (although follow-up is less complete). Of the patients who stopped in the first year, 54% were due to AEs, 23.4% PDRT and 13% PDCLL. After year 1, the proportion stopping due to AEs and PDRT fell to 40% and 19.6%, whereas the proportion stopping due to PDCLL increased to 29.4%.Within the first year, there was no access to venetoclax in the UK and Ireland and all 10 patients who stopped ibrutinib due to PDCLL died with a median survival of 33 days (0-360). Beyond the first year, 15 patients stopped ibrutinib due to PDCLL. of these, 5 have died (managed with palliative care (n = 3), idelalisib/rituximab (n = 1), no data (n = 1)) and 10 are still alive. of these 10, 1 has been treated with R-idelalisib (34 days post ibrutinib cessation), and 9 have been treated with venetoclax with a median follow-up of 107 days (9-498) post ibrutinib. Four other patients who stopped ibrutinib for non-PDCLL reasons have also been treated with venetoclax, with (Figure Presented) 2 still alive on therapy. Figure 1B compares the OS of patients who stopped ibrutinib for PDCLL within the first year and beyond 1 year. There is a marked survival advantage for patients relapsing beyond 1 year with over 60% reduction in the risk of death (HR: 0.33 (0.11-0.98); p = 0.0333). In contrast, patients stopping ibrutinib for all other reasons show no survival difference whether they stop within the first year or beyond. Conclusions: While the relative rate of ibrutinib discontinuation reduces with time on therapy, the proportion stopping for PDCLL increases. OS appears best for patients who stop for non-infectious AEs and for PDCLL patients, survival appears better if progression occurs later. This may partly reflect biologically less aggressive disease, although access to venetoclax for patients relapsing beyond one year is also likely to have been significant.