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Discontinuation of Ibrutinib Is Common in Older Patients With CLL, Study Finds


Patients with chronic lymphocytic leukemia (CLL) who discontinued ibrutinib had higher rates of adverse events compared with those who continued the therapy, the authors found.

Real-world data on older patients with chronic lymphocytic leukemia (CLL) suggest that there is a significant unmet need in terms of managing adverse events (AEs) in patients taking ibrutinib (Imbruvica; Pharmacyclics/Janssen).

Chronic lymphocytic leukemia cells in blood flow | Image Credit: © LASZLO - stock.adobe.com

Chronic lymphocytic leukemia cells in blood flow | Image Credit: © LASZLO - stock.adobe.com

The report, which was based on Medicare beneficiary data and published in the journal Cancer Medicine, found nearly two-thirds of patients who initiated the therapy appeared to have discontinued it within about 2 years. Those who discontinued within 12 months had a significantly higher rate of AEs compared with patients who did not discontinue and those who discontinued after 12 months, the authors noted.

The researchers wrote that ibrutinib has led to a new paradigm in the treatment of CLL, improving both progression-free survival and overall survival compared with chemotherapy.

“However, clinical studies have shown several adverse events to be associated with ibrutinib use, some of which can lead to treatment discontinuation,” the authors explained. “Ibrutinib-related AEs are a more common reason for its discontinuation in the real-world setting than in clinical trials.”

Although the issue of AEs is well known, most of the existing literature consists of research from academic medical centers or population-based studies of commercially insured patients. Thus, they said, relatively little is known about AE risk among older patients specifically.

In order to get a better understanding of AEs among older patients, who are more likely to be frail or have multiple comorbidities, the investigators used Medicare claims data from 2013-2019 to identify 11,870 Medicare beneficiaries who had CLL and began treatment with ibrutinib. The cohort had a mean age of 77.2 years, 58.5% were male, and 90.1% were White.

The authors found that 65.2% of patients had evidence of discontinuing ibrutinib by a median follow-up period of 2.3 years. The rest of the cohort appeared to continue with the therapy. The largest group of patients (45.1%) discontinued within 12 months of starting the therapy; 20.1% discontinued after more than 12 months; and 34.8% were still on the treatment by the end of the follow-up period, the authors said.

Among patients who appeared to discontinue ibrutinib, the rate of reported AEs was 62.5 AEs per 1000 patient-months. For patients who did not discontinue, the rate was 32.9 AEs per 1000 patient-months. However, when the authors looked more closely at the AE rate among patients who discontinued, they found those who discontinued within 12 months had an AE rate of 140.2 per 1000 patient-months, whereas those who discontinued after 12 months had an AE rate of 34.5 AEs per 1000 patient-months, a rate similar to that of the nondiscontinuers.

The most common AEs were hematologic AEs, such as anemia and thrombocytopenia, and nonhematologic AEs, including infections, arthralgia/myalgia, and cardiovascular events like atrial fibrillation and heart failure. The investigators noted that their AE data only include new cases of comorbidities, meaning that patients who had preexisting cardiovascular issues, for instance, would not be reflected in these numbers.

“However, it is possible that the use of ibrutinib in these patients worsened preexisting comorbidities (eg, hypertension or atrial fibrillation),” they wrote. “Hence, additional efforts are needed to examine the ibrutinib-related AE experience of patients with such pre-existing comorbidities and identify best management practices.”

The investigators noted that their data set has notable limitations. As with any claims database, coding errors could be included and potentially affect the results. In addition, they classified patients as having discontinued ibrutinib if they found a 60-day consecutive gap in ibrutinib treatment. However, they wrote, “we could not account for phenomena such as dose modification wherein a provider may ask a patient to extend their existing prescription, thus extending the days' supply beyond what would be indicated on the claim.” They also did not have data on the reasons for discontinuation.

The investigators concluded, however, that the existing data suggest new treatments may be needed to improve outcomes in this patient population. They also said more work needs to be done to better understand how to manage AEs in these patients.


Huntington SF, de Nigris E, Puckett JT, et al. Real-world analysis of adverse event rates after initiation of ibrutinib among Medicare beneficiaries with chronic lymphocytic leukemia. Cancer Med. 2024;13(2):e6953. doi:10.1002/cam4.6953

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