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A real-world study to assess the association of cardiovascular adverse events (CVAEs) with ibrutinib as first-line (1L) treatment for patients with chronic lymphocytic leukaemia (CLL) in the United States.

ABSTRACT: Ibrutinib, a Bruton's tyrosine kinase inhibitor, is often used as first-line (1L) treatment of chronic lymphocytic leukaemia (CLL); however, it is associated with an increased risk for cardiovascular adverse events (CVAEs). This real-world study adds to existing literature by simultaneously investigating the correlation between pre-existing CV risk factors and the relative cardiotoxicity of ibrutinib vs other therapies in CLL/small lymphocytic lymphoma (SLL). Using a real-world database, the risk of subsequent CVAEs (any CVAE, atrial fibrillation [AF], or hypertension) were compared among patients who received 1L ibrutinib monotherapy or another type of non-ibrutinib therapy, grouped as intensive (IT) or non-intensive therapy (NIT). Each patient's baseline CV risk was estimated using the Framingham risk score. Inverse probability treatment weighting was incorporated into a logistic regression model to reduce baseline imbalance. Results showed ibrutinib was significantly associated with higher risk of CVAEs regardless of baseline CV risk. Compared with IT, odds ratios of any CVAE, hypertension, or AF were 2.61, 3.66, and 3.02, respectively vs 1.88, 2.13, and 2.46, respectively, with NIT. Sensitivity analyses confirmed the findings were robust. These results suggest clinical caution should be taken when selecting ibrutinib for patients with CLL/SLL, especially in those with high baseline CV risk.

SUBMITTER: Mato A

PROVIDER: S-EPMC9928661 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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A real-world study to assess the association of cardiovascular adverse events (CVAEs) with ibrutinib as first-line (1L) treatment for patients with chronic lymphocytic leukaemia (CLL) in the United States.

Mato Anthony A Tang Boxiong B Azmi Soraya S Yang Keri K Han Yi Y Zhang Xiaowei X Roeker Lindsey L Wallis Nicola N Stern Jennifer C JC Hedrick Eric E Huang Jane J Sharman Jeff P JP

EJHaem 20230123 1

Ibrutinib, a Bruton's tyrosine kinase inhibitor, is often used as first-line (1L) treatment of chronic lymphocytic leukaemia (CLL); however, it is associated with an increased risk for cardiovascular adverse events (CVAEs). This real-world study adds to existing literature by simultaneously investigating the correlation between pre-existing CV risk factors and the relative cardiotoxicity of ibrutinib vs other therapies in CLL/small lymphocytic lymphoma (SLL). Using a real-world database, the ris ...[more]

PMID: 36819172

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Project description: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.

Project description:BackgroundIbrutinib, an inhibitor of Bruton's tyrosine kinase, and venetoclax, an inhibitor of B-cell lymphoma 2 protein, have been approved for patients with chronic lymphocytic leukemia (CLL). Preclinical investigations have indicated potential synergistic interaction of their combination.MethodsWe conducted an investigator-initiated phase 2 study of combined ibrutinib and venetoclax involving previously untreated high-risk and older patients with CLL. All patients had at least one of the following features: chromosome 17p deletion, mutated TP53, chromosome 11q deletion, unmutated IGHV, or an age of 65 years or older. Patients received ibrutinib monotherapy (420 mg once daily) for 3 cycles, followed by the addition of venetoclax (weekly dose escalation to 400 mg once daily). Combined therapy was administered for 24 cycles. Response assessments were performed according to International Workshop on Chronic Lymphocytic Leukemia 2008 criteria. Minimal residual disease was assessed by means of multicolor flow cytometry in bone marrow (sensitivity, 10-4).ResultsA total of 80 patients were treated. The median age was 65 years (range, 26 to 83). A total of 30% of the patients were 70 years of age or older. Overall, 92% of the patients had unmutated IGHV, TP53 aberration, or chromosome 11q deletion. With combined treatment, the proportions of patients who had complete remission (with or without normal blood count recovery) and remission with undetectable minimal residual disease increased over time. After 12 cycles of combined treatment, 88% of the patients had complete remission or complete remission with incomplete count recovery, and 61% had remission with undetectable minimal residual disease. Responses were noted in older adults and across all high-risk subgroups. Three patients had laboratory evidence of tumor lysis syndrome. The adverse-event profile was similar to what has been reported with ibrutinib and venetoclax.ConclusionsIn this study, combined venetoclax and ibrutinib was an effective oral regimen for high-risk and older patients with CLL. (Funded by AbbVie and others; ClinicalTrials.gov number, NCT02756897.).

Project description:Objectives: The SRealCLL study described the occurrence of adverse events (AEs) and healthcare resource utilization in patients with chronic lymphocytic leukaemia (CLL) using artificial intelligence in a real-world scenario in Spain. Methods: We collected real-world data on patients with CLL from seven Spanish hospitals between January 2016 and December 2018, focusing on their AE and healthcare service utilization. Data extraction from electronic health records of 385,904 patients was performed using the EHRead® technology, which is based on natural language processing and machine learning. Results: Among the 534 CLL patients finally included, 270 (50.6%) were categorized as watch and wait (W&W), 230 (43.1%) as first-line treatment (1L), and 58 (10.9%) as relapse/refractory with second-line treatment (2L). The median study follow-up periods were 14.4, 8.4, and 6 months for W&W, 1L, and 2L, respectively. The most common antineoplastic treatments were ibrutinib (64.8%) and bendamustine + rituximab (12.6%) in 1L, and ibrutinib (62.1%) and venetoclax (15.5%) in 2L. Among the most frequent AEs, anaemia and thrombocytopenia presented higher rates in the treated groups (1L and 2L) compared with W&W (2.01 and 2.32 vs. 0.93; p ≤ 0.05 and 1.29 and 1.62 vs. 0.42; p ≤ 0.05). Moreover, several AEs, such as major bleeding, digestive symptoms, general symptoms, or Richter syndrome, were more frequent in 1L than W&W (all p ≤ 0.05). No differences were shown between groups in the rates of outpatient visits. However, rates of outpatient visits due to AE were higher in 1L than in W&W (1.07 vs. 0.65, p ≤ 0.05). The rates of patients being hospitalized were higher in the treated groups compared to W&W (1.68 and 1.9 vs. 0.88; p ≤ 0.05), and those due to AE were higher in 1L than W&W (1.23 vs. 0.60; p ≤ 0.05). Conclusions: Patients with CLL in 1L or 2L treatments often require healthcare resources due to AEs, particularly cytopenias. The methodology used in this study likely enabled us to identify higher rates of AEs that may be underreported using other real-world approaches. Addressing AEs with effective agents that maximize patient safety and optimize healthcare resource use is crucial in this typically older and comorbid population.

Dataset Information

A real-world study to assess the association of cardiovascular adverse events (CVAEs) with ibrutinib as first-line (1L) treatment for patients with chronic lymphocytic leukaemia (CLL) in the United States.

Publications

A real-world study to assess the association of cardiovascular adverse events (CVAEs) with ibrutinib as first-line (1L) treatment for patients with chronic lymphocytic leukaemia (CLL) in the United States.

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