Real-World Clinical Outcomes and Adverse Events in Patients with Chronic Lymphocytic Leukemia Treated with Ibrutinib: A Single-Center Retrospective Study

Abstract

Background and Objectives: The treatment of chronic lymphocytic leukemia (CLL) has acquired new targeted therapies. In clinical trials, ibrutinib improved outcomes safely. Real-world data called for a reappraisal of ibrutinib strategies. We report on a single center’s experience with ibrutinib monotherapy, aiming to explore the outcomes, tolerability, and prognosis of CLL patients in routine clinical practice. Materials and Methods: Data were collected from all CLL patients treated with ibrutinib at Fundeni Clinical Institute, Bucharest, Romania, between January 2016 and June 2021. Results: A total of one hundred twenty-three CLL adult patients were treated with ibrutinib. Of the patients, 87% had relapsed/refractory CLL. The median age at ibrutinib initiation was 65 years; 44.7% of patients were staged Rai III/IV. At 32-month median follow-up, the median progression-free survival (PFS) was 50 months, the overall survival (OS) was not reached, and the overall response rate (ORR) was 86.2%. The age or number of previous therapies did not impact outcomes or tolerability. An Eastern Cooperative Oncology Group performance status (ECOG PS) score ≥ 2 and shorter time from initiation of last therapy (TILT) before ibrutinib predicted inferior PFS. Baseline characteristics had no impact on the OS except for TILT in R/R CLL patients. Drug-related adverse events (AEs) of any grade and grade ≥ 3 AEs were reported in 82.1% and 30.9% of the patients, respectively. Infections were the most common AEs (29.3%). Drug discontinuation was permanent in 43.9% of patients, mainly due to disease progression (17.1%) and toxicity (8.9%). Patients with a Cumulative Illness Rating Scale (CIRS) score ≥ 6 had a higher risk for toxicity-related discontinuation. An ECOG PS ≥ 2 predicted an increased rate of permanent discontinuation and grade ≥ 3 AEs. Conclusions: The outcomes of this study align with the results from ibrutinib clinical trials. Our study demonstrated that poor patient fitness, early relapse before ibrutinib, and permanent ibrutinib discontinuation are essential outcome determinants. Patient comorbidity burden and fitness were significant predictors for ibrutinib intolerance.

Incidence of cardiovascular and bleeding events and reasons for discontinuation in patients with chronic lymphocytic leukemia treated with ibrutinib—A retrospective analysis on consecutive patients from a well‐defined region

“…In previously published real‐world studies with varying follow‐up times, the majority shorter than ours, the incidence ranged between 3% and 17%. In these studies, AF was reported as cumulative incidence at the end of follow up, and therefore a direct comparison with our data is not always possible 6,18,20,21,24–26 . Also, real‐world data from long‐term follow‐up are limited.…”

“…However, only 9% of the patients discontinued due to toxicity while in our study 25% did, which could be explained by the older age and higher comorbidity of the patients in our cohort. Data from other studies are discordant, with either toxicity 6,20,22 or progressive disease 18,19,21 reported as the most frequent reason for discontinuation.…”

“…In real‐world studies with a median follow‐up shorter than 2 years, discontinuation rates have been reported to range from 15% to 42% 6,18–20 . In one study conducted by Moldovianu et al, with a median follow‐up time of 32 months (range 22–51), 44% of the patients discontinued treatment 21 . However, only 9% of the patients discontinued due to toxicity while in our study 25% did, which could be explained by the older age and higher comorbidity of the patients in our cohort.…”

“…In these studies, AF was reported as cumulative incidence at the end of follow up, and therefore a direct comparison with our data is not always possible. 6,18,20,21,[24][25][26] Also, real-world data from long-term follow-up are limited. However, in a prospective study in which patients were monitored with ECG at least every third month, the cumulative incidence was reported to be 38% at 2 years.…”