Patients with CLL face ‘substantial burden’ of adverse events in real-world treatment setting
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ORLANDO — Adverse events from treatment for chronic lymphocytic leukemia appeared common among Medicare patients treated in a real-world setting, which contributed to a substantial economic burden for these patients, according to results of a population-based retrospective cohort study presented at ASH Annual Meeting and Exposition.
“CLL is the most common type of leukemia, representing one-third of all newly diagnosed leukemia cases in the U.S.,” James A. Kaye, MD, DrPH, senior director of epidemiology at RTI Health Solutions, said during his presentation. “However, data on OS and adverse events are mostly available from controlled trials. Information from routine clinical practice is sparse, particularly in older populations.”
Kaye and colleagues sought to describe characteristics, treatments, OS, adverse events and the economic burden of patients with CLL receiving therapy, and to explore the association between the number of adverse events and health care costs.
Researchers used the Medicare claims database to identify 7,965 patients (median age, 76 years) who received at least one systemic therapy for CLL between 2013 and 2015 and who had at least 18 months of continuous Medicare enrollment. Follow-up continued through 2016, the most recent year for which data were available from the Medicare database.
Researchers defined the first observed therapy as all agents received on or within 35 days of receipt of the first systemic drug for CLL.
“‘First observed therapy’ may not necessarily represent ‘first-line therapy,’ as data available for this study may not contain information on some patients with prior treatments, despite having at least 18 months of treatment documented in the database,” Kaye said. “This may be the case for patients who had earlier treatment through private insurance prior to Medicare or if they participated in a clinical trial.”
Common treatment regimens included ibrutinib (Imbruvica; Janssen, Pharmacyclics; 26%), chlorambucil (19%), bendamustine/rituximab (Rituxan; Genentech, Biogen; 16%) or rituximab alone (13%); 25% of patients received other therapies.
Researchers noted that patients who received ibrutinib (mean age, 75.2 years; 60.6% men) or bendamustine/rituximab (mean age, 74.5 years; 61.8% men) were younger at the start of treatment and more likely to be male than those in the other treatment groups.
Median follow-up from the start of first observed therapy was 19 months for patients receiving ibrutinib, 21 months for patients receiving chlorambucil and 24 months for patients receiving bendamustine/rituximab.
Median OS was 40.8 months (95% CI, 38.6-not reached) for patients who received chlorambucil and not reached for the other treatment groups.
Researchers reported 2-year OS rates of 69% (95% CI, 68-71) for ibrutinib, 68% (95% CI, 65-71) for chlorambucil and 79% (95% CI, 77-81) for bendamustine/rituximab.
When looking at adverse events, researchers noted that neutropenia was more common among patients who received bendamustine/rituximab, as were dehydration and nausea and vomiting. Thrombocytopenia, atrial fibrillation, bleeding and renal failure were more common among those treated with ibrutinib. Treatment with chlorambucil and rituximab alone did not stand out as being associated with any adverse events to a greater degree than the other treatments, Kaye said.
Researchers also evaluated the economic burden of initial treatment for CLL and found that mean monthly costs per patient were $1,865 (standard deviation [SD], $2,347) at baseline and $8,798 (SD, $11,063) during the period after initiation of the first systemic therapy for CLL.
Mean monthly costs also correlated with the occurrence of adverse events, with costs ranging from $5,144 (SD, $5,409) among those with one to two adverse events to $10,077 (SD, $12,542) among those with six or more adverse events.
Patients with three or more adverse events incurred 4.7 times (95% CI, 4.4-5.05) the costs of patients with fewer events, which is likely related to health care resource use and hospital stays, Kaye said.
Costs also tended to be lower among the other treatment groups compared with those who received ibrutinib, he added.
“These rates of adverse events highlight a substantial burden among Medicare patients treated in real-world setting,” Kaye said. “Our findings also demonstrate a considerable economic burden, which increases with the number of adverse events.” – by Alexandra Todak
Reference:
Goyal RK, et al. Abstract 796. Presented at: ASH Annual Meeting and Exposition; Dec. 7-10, 2019; Orlando.
Disclosures: Kaye reports employment with RTI Health Solutions and research funding form AstraZeneca. Please see the abstract for all other authors’ relevant financial disclosures.
Perspective
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James Gerson, MD
This trend has been well-described for many years in countless disease sites where the patients who are eligible for clinical trials are a very special population. People have to be healthy enough to get into the trial, to travel to the site and to wait for the screening procedures, so it tends to be a very cream-of-the-crop-type population.
That leads to challenges when agents get approved and are taken up in the community, because community clinicians will come back to us and say the patients they see are often a more challenging population. It can be very challenging to extrapolate clinical trial data to patients who are really sick, elderly, have comorbidities and can’t tolerate the therapies often employed in clinical trials.
It’s really important to have a data set large enough to show an experience, especially in a community setting. These are pooled data, so it’s not just academic-center patients, but those in the real world.
We’ve known that patients in the community tend to have more adverse events, but we didn’t really know how to manage those adverse events. Now there are well-established data about methods to decrease toxicity, such as holding doses or even decreasing doses, sometimes in a scheduled fashion. The biggest take-home for community practitioners is to think about your patients early on as having the potential for adverse events and to follow some of the early dose de-escalation strategies that have been published previously. For instance, a data set with ibrutinib showed that over the course of 3 months, you can taper treatment from three tabs to one tab in a scheduled fashion with no change in efficacy and much lower rates of adverse events.
The challenge I had with this paper is interpreting what the economic burden really meant, because these huge database studies do not show you the source of the costs. Were they because patients were referred to specialist or taking additional medications to manage the side effects? Did they have more hospitalizations? It is hard to tell what drove the increased costs and whether it’s actually just a marker of a sicker population. People who are sick have higher costs, so maybe it’s not that the adverse events led to higher costs, but rather the patient population itself.
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