Medicare Patients With CLL Continue to Face High Costs Related to AEs

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More than two-thirds of patients with chronic lymphocytic leukemia (CLL) survived at least 2 years but were highly susceptible to adverse events (AEs), in a recent study.

Following initiation of treatment for chronic lymphocytic leukemia (CLL), more than two-thirds of patients survived for at least 2 years, but not without high susceptibility to adverse events (AEs), according to a new study.

The majority of patients (74.5%) had at least 6 AEs during CLL treatment, and 20.1% had 3 to 5 AEs, according to the study published in Cancer Medicine. Further analysis shows that patients in these groups were associated with a 37 times’ greater risk of becoming an inpatient—at nearly 5 times the monthly costs—than those with fewer AEs during the first line of therapy.

“[T]hese findings suggest the need to explore and better understand AE consequences and develop therapeutic alternatives that potentially induce fewer toxicities and that may offer improved clinical outcomes at lower costs,” wrote the authors, who were from RTI Health Solutions and AstraZeneca.

The goal of their study was to supplement scarce real-world data on Medicare patients.

CLL is the most common type of leukemia, representing 37% of all newly diagnosed cases in the Unites States. The median age of diagnosis ranges from 70 to 72 years.


The disease typically progresses slowly, with treatment initiated only as symptoms develop and clinical evidence of disease progression becomes apparent. The cost burden in the United States for CLL is projected to increase from about $740 million in 2011 to more than $5 billion by 2025.

The CLL-related death rate decreased by about 3% annually between 2006 and 2015, but the number of cases shot up from 7300 in 1998 to 20,940 in 2018, likely owing to the aging population, the authors said.

Most CLL data on overall survival (OS) and AEs in the present study are from clinical trials. This retrospective study reviewed data on 7965 patients receiving systemic therapy from 2013 to 2015, from the beginning of therapy through December 2016 or death.

The results indicate that the most common treatments for CLL were bendamustine plus rituximab (BR; 79%), followed by ibrutinib (69%) and chlorambucil monotherapy (68%). The most frequently reported AEs were neutropenia, hypertension, anemia, and infection.

Neutropenia was more common in the BR group, along with dehydration, nausea, or vomiting. The ibrutinib group more commonly had low platelet counts, atrial fibrillation, bleeding, pneumonia, and renal failure. Anemia, a frequent manifestation of CLL, was common in all groups.

Two-year OS in the Medicare data was significantly lower that than seen in clinical trials for most treatments. The study found that OS for the Medicare population ranged from 68% to 79% compared with 95% for BR and 90% for ibrutinib in the first-line setting; in the relapsed/refractory setting, OS was 80% for BR and nearly 83% for ibrutinib.

Mean monthly all-cause costs rose sharply in relation to the number of AEs, the study found: from $5144 among those with 1 to 2 AEs to $10,077 among those with 6 or more. The overall average was $8974, and the extrapolated annual cost was about $106,000, driven primarily by inpatient admissions, office visits, and outpatient prescription drugs.

The mean costs were higher for those on ibrutinib. Furthermore, AEs were consistently higher for ibrutinib, the only Bruton’s tyrosine kinase inhibitor available at the time of the study. Those treated with BR, rituximab, and chlorambucil had lower odds of inpatient admission as well as lower monthly costs in comparison to ibrutinib.

The authors suggest these findings reflect a potentially higher disease burden in those treated with ibrutinib, that these patients are frail, and that patients who have Medicare coverage continue to have unmet medical needs.

“Medicare incurs substantial economic burden following initiation of systemic therapy for CLL, and greater numbers of AEs were associated with higher overall cost of CLL management,” they conclude. “The study findings highlight considerable susceptibility to AEs and an unmet medical need in Medicare patients with CLL treated in routine practice.”


Goyal RK, Nagar SP, Kabadi SM, Le H, Davis KL, Kaye JA. Overall survival, adverse events, and economic burden in patients with chronic lymphocytic leukemia receiving systemic therapy: Real‐world evidence from the Medicare population. Cancer Med. Published online March 18, 2021. doi:10.1002/cam4.3855