Real-World Persistence and Time to Next Treatment With Ibrutinib in Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma Including Patients at High Risk for Atrial Fibrillation or Stroke

Narezkina, Anna; Akhter, Nausheen; Lu, Xiaoxiao; Émond, Bruno; Panjabi, Sumeet; Forbes, Shaun P.; Hilts, Annalise; Liu, Stephanie; Lafeuille, Marie-Hélène; Lefèbvre, Patrick; Huang, Qing; Choi, Michael Y.

doi:10.1016/j.clml.2022.07.004

Cited by 8 publications

(8 citation statements)

References 45 publications

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“…However, whether the occurrence of IRAF impacts upon prognosis is still under investigation, with some groups reporting lower PFS and OS and others showing no impact of IRAF upon survival. 17,28 As per institutional practice, none of our patients experienced ibrutinib dose reductions following the diagnosis of IRAF, with a dose intensity of 100% and with survival outcomes comparable to those reported in literature; further studies are needed to define the effective need for dose reductions in patients experiencing AF and subsequent impact on prognosis. 29 As said, the management of AF in these patients requires a close cooperation between the hematologist and an expert cardiooncologist, also considering the anti-platelets effect of ibrutinib and its subsequent possibly increased risk of bleeding.…”

Section: Discussionmentioning

confidence: 59%

“…Among ibrutinib‐related toxicities, AF is associated with an increased risk of stroke and thromboembolism, which can lead to significant morbidity and mortality. However, whether the occurrence of IRAF impacts upon prognosis is still under investigation, with some groups reporting lower PFS and OS and others showing no impact of IRAF upon survival 17,28 …”

Section: Discussionmentioning

confidence: 99%

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Predictors of ibrutinib‐associated atrial fibrillation: 5‐year follow‐up of a prospective study

Mattiello

Barone

Giannarelli

et al. 2023

Hematological Oncology

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Ibrutinib‐associated atrial fibrillation (IRAF) emerged among the adverse events of major interests in ibrutinib‐treated patients as real‐world studies showed a higher incidence compared to clinical trials. We prospectively analyzed predictors of IRAF in 43 single‐center consecutive patients affected by chronic lymphocytic leukemia that started therapy with ibrutinib between 2015 and 2017. Key secondary endpoints were to describe the management of IRAF and survival outcomes. During a median follow‐up period of 52 months, we registered 45 CV events, with a total of 23 AF events in 13 patients (CI 30.0% (95% CI: 16.5–43.9)). Pre‐existent cardiovascular risk factors, in particular hypertension, a previous history of AF and a high Shanafelt risk score emerged as predictors of IRAF. Baseline echocardiographic evaluation of left atrial (LA) dimensions confirmed to predict IRAF occurrence and cut‐off values were identified in our cohort: 32 mm for LA diameter and 18 cm2 for LA area. No difference in progression free survival and overall survival emerged in patients experiencing IRAF. Following AF, anticoagulation was started in all eligible patients, and cardioactive therapy was accordingly modified. Echocardiography represents a highly reproducible and widespread tool to be included in the work‐up of ibrutinib candidates; the identification of IRAF predictors represents a useful guide to clinical practice.

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Section: Discussionmentioning

confidence: 59%

Section: Discussionmentioning

confidence: 99%

Predictors of ibrutinib‐associated atrial fibrillation: 5‐year follow‐up of a prospective study

Mattiello

Barone

Giannarelli

et al. 2023

Hematological Oncology

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“…Moreover, 85.6% of ibrutinib-treated patients experienced grade ≥ 3 AEs, and overall, these data show that there is considerable susceptibility to AEs in Medicare patients with CLL in the U.S. Interestingly, 2190 patients treated with first-line ibrutinib were analyzed using a nationwide U.S. electronic health record-derived database. TTNT with ibrutinib was not significantly different in patients with a high-risk cardiovascular profile, with a TTD in all patients of 15.7 months, as compared with 11.7 and 13.7 months in patients with high AFib risk and high stroke risk, respectively [77].…”

Section: Real-world Evidencementioning

confidence: 72%

First-Line Treatment of Older Patients with CLL: A New Approach in the Chemo-Free Era

Urso,

Cavazzini,

Ballardini

et al. 2023

Cancers

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Bruton tyrosine kinase inhibitors (BTKi) and the BCL2 inhibitor venetoclax, with or without the anti-CD20 monoclonal antibody Obinutuzumab, represent the preferred options for the first-line therapy of CLL because they are more effective and may improve quality of life. However, patient inclusion criteria are heterogeneous across trials designed for older patients, and the identification of CLL-specific parameters identifying unfit patients at risk of developing drug-specific adverse events is required to guide treatment choice. Due to inclusion/exclusion criteria in trials, higher discontinuation rates with BTKi were reported in real-world studies, and registry analyses provided useful information on factors predicting earlier discontinuation in a real-world setting. Though targeted agents were shown to be cost-effective treatments in high-income countries, the out-of-pocket expenses may limit accessibility to these drugs, and the overall expenditure for new drugs in CLL is projected to increase substantially, posing an issue for sustainability. This being said, the choice of a finite-duration treatment based on venetoclax-containing regimens or treatment until progression with BTKi is today possible in high-income countries, and the therapy choice drivers are represented by coexisting medical conditions rather than age, patient expectations, logistics, and sustainability.

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“…More importantly, even though the pivotal RESONATE‐2 study encompassed patients up to 80 years of age, it did not provide specific details about this particular elderly subgroup 3,4 . Likewise, real‐world evidence investigating the effectiveness and safety of ibrutinib in the elderly, involved patients with a median age ranging from 69 to 75 years 15–18 . A recent Italian retrospective study assessed the effectiveness and safety profile of ibrutinib in a cohort of R/R and TN CLL patients over the age of 80.…”

Section: Discussionmentioning

confidence: 99%

“…3,4 Likewise, realworld evidence investigating the effectiveness and safety of ibrutinib in the elderly, involved patients with a median age ranging from 69 to 75 years. [15][16][17][18] A recent Italian retrospective study assessed the effectiveness and safety profile of ibrutinib in a cohort of R/R and TN CLL patients over the age of 80. The analysis revealed that the only factor influencing PFS was the response achievement 5 Importantly, the safety profile observed in this study remained consistent with existing literature data with no unexpected AEs reported.…”

Section: Safetymentioning

confidence: 99%

Ibrutinib as first line therapy in chronic lymphocytic leukemia patients over 80 years old: A retrospective real‐life multicenter Italian cohort

Martino,

Mauro,

Reda

et al. 2024

Hematological Oncology

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Although chronic lymphocytic leukemia (CLL) predominantly affects the elderly, limited data exists about the outcomes of over 80‐year‐old patients, usually underrepresented in clinical trials. We conducted a multicenter study enrolling 79 consecutive CLL patients ≥80 years at the time of frontline therapy, all treated with ibrutinib. Nearly 48% of cases exhibited unmutated IGHV genes, 32% 17p deletion, and 39.2% TP53 mutations; 63.3% displayed a cumulative illness rating scale (CIRS) > 6. The overall response rate on ibrutinib, computed in 74/79 patients (5 patients excluded for early withdrawal), was 89.9%. After a median follow‐up of 28.9 months, the median progression‐free survival (PFS) and overall survival (OS) were 42.5 and 51.8 months, respectively. CIRS>6 and temporary discontinuation of ibrutinib lasting for 7–30 days were the only parameters associated with a significantly shorter PFS and were both relevant in predicting a shorter PFS compared to patients with CIRS≤6 and therapy discontinuation ≤7 days. The most common grade≥3 adverse events were infections (25.5%), neutropenia (10.1%), and anemia (2.5%). Eighteen patients (22.8%) experienced a cardiovascular event, including grade‐2 atrial fibrillation (n = 9; 11%), grade‐2 hypertension (n = 5; 6%), heart failure (n = 3; 3%), and acute coronary syndrome (n = 1; 1%). Mild bleeding events were observed in 27 patients (34.2%). Ibrutinib was permanently discontinued in 26 patients due to progressive disease (n = 11, including 5 Richter's syndromes), secondary malignancies (n = 6), infections (n = 3), cardiac failure (n = 3), severe bleeding (n = 2), and sudden death (n = 1). In conclusion, our analyses confirmed the overall effectiveness and favorable safety profile of the ibrutinib‐single agent therapeutic approach in CLL patients ≥80 years.

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Real-World Persistence and Time to Next Treatment With Ibrutinib in Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma Including Patients at High Risk for Atrial Fibrillation or Stroke

Cited by 8 publications

References 45 publications

Predictors of ibrutinib‐associated atrial fibrillation: 5‐year follow‐up of a prospective study

Predictors of ibrutinib‐associated atrial fibrillation: 5‐year follow‐up of a prospective study

First-Line Treatment of Older Patients with CLL: A New Approach in the Chemo-Free Era

Ibrutinib as first line therapy in chronic lymphocytic leukemia patients over 80 years old: A retrospective real‐life multicenter Italian cohort

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