Dataset Information

Real-world analysis of adverse event rates after initiation of ibrutinib among Medicare beneficiaries with chronic lymphocytic leukemia.

ABSTRACT:

Background

The first-generation BTK inhibitor ibrutinib is a standard-of-care therapy in the treatment of chronic lymphocytic leukemia (CLL) despite potential side effects that often lead to discontinuation.

Methods

This study used 2013-2019 claims data to describe the incidence rate of adverse events (AEs) among elderly Medicare beneficiaries newly initiating ibrutinib for CLL.

Results

The final sample contained 11,870 Medicare beneficiaries with CLL (mean age 77.2) newly initiating ibrutinib, of whom 65.2% discontinued over mean follow-up of 2.3 years. The overall incidence rate of AEs was 62.5 per 1000 patient-months for all discontinuers and 32.9 per 1000 patient-months for non-discontinuers. Discontinuers had a higher incidence rate of AEs per 1000 patient-months compared with non-discontinuers for all AEs examined, including infection (22.8 vs. 14.5), atrial fibrillation (15.1 vs. 7.0), anemia (21.9 vs. 14.5), and arthralgia/myalgia (19.5 vs. 13.6).

Conclusion

In this first real-world study of a national sample of elderly US patients treated with ibrutinib, we found a clear unmet need for improved management of ibrutinib-related AEs and/or new treatments to improve real-world outcomes in patients with CLL.

SUBMITTER: Huntington SF

PROVIDER: S-EPMC10832339 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

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Publications

Real-world analysis of adverse event rates after initiation of ibrutinib among Medicare beneficiaries with chronic lymphocytic leukemia.

Huntington Scott F SF de Nigris Enrico E Puckett Justin T JT Kamal-Bahl Sachin S Farooqui Mohammed M Ryland Katherine K Sarpong Eric M EM Leng Siyang S Yang Xiaoqin X Doshi Jalpa A JA

Cancer medicine 20240101 2

<h4>Background</h4>The first-generation BTK inhibitor ibrutinib is a standard-of-care therapy in the treatment of chronic lymphocytic leukemia (CLL) despite potential side effects that often lead to discontinuation.<h4>Methods</h4>This study used 2013-2019 claims data to describe the incidence rate of adverse events (AEs) among elderly Medicare beneficiaries newly initiating ibrutinib for CLL.<h4>Results</h4>The final sample contained 11,870 Medicare beneficiaries with CLL (mean age 77.2) newly ...[more]

PMID: 38348963

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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:BackgroundData regarding the efficacy of treatment with ibrutinib-rituximab, as compared with standard chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab, in patients with previously untreated chronic lymphocytic leukemia (CLL) have been limited.MethodsIn a phase 3 trial, we randomly assigned (in a 2:1 ratio) patients 70 years of age or younger with previously untreated CLL to receive either ibrutinib and rituximab for six cycles (after a single cycle of ibrutinib alone), followed by ibrutinib until disease progression, or six cycles of chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab. The primary end point was progression-free survival, and overall survival was a secondary end point. We report the results of a planned interim analysis.ResultsA total of 529 patients underwent randomization (354 patients to the ibrutinib-rituximab group, and 175 to the chemoimmunotherapy group). At a median follow-up of 33.6 months, the results of the analysis of progression-free survival favored ibrutinib-rituximab over chemoimmunotherapy (89.4% vs. 72.9% at 3 years; hazard ratio for progression or death, 0.35; 95% confidence interval [CI], 0.22 to 0.56; P<0.001), and the results met the protocol-defined efficacy threshold for the interim analysis. The results of the analysis of overall survival also favored ibrutinib-rituximab over chemoimmunotherapy (98.8% vs. 91.5% at 3 years; hazard ratio for death, 0.17; 95% CI, 0.05 to 0.54; P<0.001). In a subgroup analysis involving patients without immunoglobulin heavy-chain variable region (IGHV) mutation, ibrutinib-rituximab resulted in better progression-free survival than chemoimmunotherapy (90.7% vs. 62.5% at 3 years; hazard ratio for progression or death, 0.26; 95% CI, 0.14 to 0.50). The 3-year progression-free survival among patients with IGHV mutation was 87.7% in the ibrutinib-rituximab group and 88.0% in the chemoimmunotherapy group (hazard ratio for progression or death, 0.44; 95% CI, 0.14 to 1.36). The incidence of adverse events of grade 3 or higher (regardless of attribution) was similar in the two groups (in 282 of 352 patients [80.1%] who received ibrutinib-rituximab and in 126 of 158 [79.7%] who received chemoimmunotherapy), whereas infectious complications of grade 3 or higher were less common with ibrutinib-rituximab than with chemoimmunotherapy (in 37 patients [10.5%] vs. 32 [20.3%], P<0.001).ConclusionsThe ibrutinib-rituximab regimen resulted in progression-free survival and overall survival that were superior to those with a standard chemoimmunotherapy regimen among patients 70 years of age or younger with previously untreated CLL. (Funded by the National Cancer Institute and Pharmacyclics; E1912 ClinicalTrials.gov number, NCT02048813.).

Project description:BackgroundInformation on overall survival (OS) and adverse events (AEs) in patients with chronic lymphocytic leukemia (CLL) is mostly available from clinical trials. We therefore conducted a population-based retrospective cohort study to assess OS, incidence of AEs, and economic burden in real-world practice among Medicare patients treated for CLL.MethodsPatients with CLL receiving ≥1 systemic therapy from 2013 to 2015 were selected from the Medicare claims database and followed from the start of first observed systemic therapy (index date) through December 2016 or death. OS for patients receiving each of the most commonly observed treatments was estimated by the Kaplan-Meier method. AEs were assessed among patients receiving these treatments across all observed lines of therapy. All-cause direct medical costs were assessed from the Medicare system perspective.ResultsAmong 7,965 eligible patients across all observed therapy lines, ibrutinib monotherapy (Ibr; n = 2,708), chlorambucil monotherapy (Clb; n = 1,620), and bendamustine/rituximab (BR; n = 1,485) were the most common treatments. For first observed therapy, 24-month OS estimates for Ibr, Clb, and BR recipients were 69% (95% CI = 68%-71%), 68% (95% CI = 65%-71%), and 79% (95% CI = 77%-81%) respectively. The most frequently recorded AEs in patients receiving these treatments in any observed line of therapy were neutropenia, hypertension, anemia, and infection. For all patients, the mean monthly all-cause cost during the follow-up period was $8,974 (SD = $11,562); cost increased by the number of AEs, from $5,144 (SD = $5,409) among those with 1-2 AEs to $10,077 (SD = $12,542) among those with ≥6 AEs.ConclusionOver two-thirds of patients survived at least 2 years after starting their first observed therapy for CLL. Our findings highlight considerable susceptibility to AEs and unmet medical need in Medicare patients with CLL treated in routine practice. Medicare incurred substantial economic burden following initiation of systemic therapy, and patients with greater numbers of AEs accounted disproportionately for the high overall cost of CLL management.

Project description:PurposeTo determine rates and risk factors associated with severe postoperative complications after cataract surgery and whether they have been changing over the past decade.DesignRetrospective longitudinal cohort study.ParticipantsA total of 221 594 Medicare beneficiaries who underwent cataract surgery during 1994-2006.MethodsBeneficiaries were stratified into 3 cohorts: those who underwent initial cataract surgery during 1994-1995, 1999-2000, or 2005-2006. One-year rates of postoperative severe adverse events (endophthalmitis, suprachoroidal hemorrhage, retinal detachment) were determined for each cohort. Cox regression analyses determined the hazard of developing severe adverse events for each cohort with adjustment for demographic factors, ocular and medical conditions, and surgeon case-mix.Main outcome measuresTime period rates of development of severe postoperative adverse events.ResultsAmong the 221 594 individuals who underwent cataract surgery, 0.5% (1086) had at least 1 severe postoperative complication. After adjustment for confounders, individuals who underwent cataract surgery during 1994-1995 had a 21% increased hazard of being diagnosed with a severe postoperative complication (hazard ratio [HR] 1.21; 95% confidence interval [CI], 1.05-1.41) relative to individuals who underwent cataract surgery during 2005-2006. Those who underwent cataract surgery during 1999-2000 had a 20% increased hazard of experiencing a severe complication (HR 1.20; 95% CI, 1.04-1.39) relative to the 2005-2006 cohort. Risk factors associated with severe adverse events include a prior diagnosis of proliferative diabetic retinopathy (HR 1.62; 95% CI, 1.07-2.45) and cataract surgery combined with another intraocular surgical procedure on the same day (HR 2.51; 95% CI, 2.07-3.04). Individuals receiving surgery by surgeons with the case-mix least prone to developing a severe adverse event (HR 0.52; 95% CI, 0.44-0.62) had a 48% reduced hazard of a severe adverse event relative to recipients of cataract surgery performed by surgeons with the case-mix most prone to developing such outcomes.ConclusionsRates of sight-threatening adverse events after cataract surgery declined during 1994-2006. Future efforts should be directed to identifying ways to reduce severe adverse events in high-risk groups.

Dataset Information

Real-world analysis of adverse event rates after initiation of ibrutinib among Medicare beneficiaries with chronic lymphocytic leukemia.

Background

Methods

Results

Conclusion

Publications

Real-world analysis of adverse event rates after initiation of ibrutinib among Medicare beneficiaries with chronic lymphocytic leukemia.

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