4CPS-177 Analysis of dose reduction of ibrutinib in chronic lymphocytic leukaemia

<h3>Background and Importance</h3> Many patients who are treated with ibrutinib require dose reduction (DR) or even discontinuation of treatment due to comorbidities, drug interactions and adverse effects (AE). This DR may lead to a compromise in treatment effectiveness of chronic lymphocytic leukaemia (CLL). <h3>Aim and Objectives</h3> The aim is to evaluate the reasons for DR of ibrutinib and consequences on effectiveness and disease progression. <h3>Material and Methods</h3> Retrospective observational study conducted between January 2017 and September 2024 in a third-level hospital. Data collected were sex, age, Eastern Cooperative Oncology Group (ECOG), Binet Staging System, line of therapy, reduced doses, reasons of DR, AE, treatment duration, response (complete or partial) and progression-free survival (PFS). Presence of high-risk cytogenetics, including patients with poor prognosis, were determined: deletion (17p) and TP53 mutation (del(17p)/mutTP53) and immunoglobulin heavy-chain variable region gene (IGHV). Data were obtained from electronic prescription with the application Prisma and electronic health records with Diraya.raya. <h3>Results</h3> Of 69 patients on treatment with ibrutinib in LLC, 35 (50.7%) had their doses reduced (median age 77.0 (IQR:74.5–85.9) years, 55.0% male). Only one patient had ECOG 1. No del (17p)/mutTP53 with unmutated IGHV was present in three patients, no de (l17p)/mutTP53 with mutated IGHV in four patients and del(17p)/mutTP53 in six patients. Binet staging classification was: A (34.3%), B (57.1%), C (5.7%) and the rest was undetermined. Ten patients started ibrutinib as a first-line treatment, 15 as a second-line, eight as a third-line and two as a fourth-line. Reduced doses were 280 mg in 23 patients and 140 mg in 12 patients. In all patients the reason for DR was AE, except for one patient who had an adverse drug interaction. The AEs were: gastrointestinal (42.8%), haemorrhages (22.8%), arthralgia (11.4%), asthenia (11.4%), thrombopenia (8.5%) and cardiac events (5.7%). The median duration of treatment with ibrutinib was 37.5 (17.9–61.8) months. Twenty-two patients achieved a complete response and the median PFS was 29.3 (IQR: 20.0–66.5) months. Seven patients died, two of them due to the disease. <h3>Conclusion and Relevance</h3> In patients requiring DR of ibrutinib, it does not influence treatment response or disease progression. However, further studies are needed to assess the possibility of optimising treatment with DR to avoid the usual AE of this drug. <h3>References and/or Acknowledgements</h3> <h3>Conflict of Interest</h3> No conflict of interest