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Older Patients With Multiple Myeloma May Be Able to Avoid Long-Term Steroid Use


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The combination of lenalidomide plus the steroid dexamethasone (together called Rd) is considered standard treatment for elderly patients with multiple myeloma. However, prolonged steroid use can be harmful for some older adults. A new study published by Larocca et al in the journal Blood found that switching select older patients to a lower dose of lenalidomide and discontinuing dexamethasone after 9 months was not only safe, but also yielded similar outcomes as compared with patients who received continuous Rd.

Multiple myeloma most commonly occurs in people older than age 60. Because of patients’ older age, they are generally more susceptible to adverse events due to a higher likelihood of having other health conditions or functional impairments.

This phase III clinical trial involved 33 medical centers in Italy and is the first to evaluate an adapted Rd treatment schedule that spares steroid use in older patients. Participants included people with newly diagnosed multiple myeloma (median age = 76) who were deemed to be at intermediate fitness for treatment, either because of their age or deficits in their ability to perform activities of daily living, such as bathing or dressing.

“[Patients with] myeloma are a very diverse population, including fit patients who may tolerate full-dose treatments, and intermediate-fit and frail patients who are more susceptible to adverse events that may negatively affect the duration and outcome of treatment due to the presence of comorbidities and functional impairments, thus requiring an adapted therapy,” said lead author Alessandra Larocca, MD, PhD, of the University of Turin. “Our study shows, for the first time, that reducing the dose or intensity of treatment is a feasible option and produces similar outcomes as standard dose treatments for intermediate-fit patients.”

Issues With Prolonged Steroid Use

Patients with multiple myeloma usually receive continuous treatment including steroids, which are typically given until a patient’s disease progresses or they are unable to tolerate the therapy, according to Dr. Larocca. But as she explained, “Prolonged steroid use is scarcely tolerated in the long term, even in younger patients, and patients may often require dose reduction or interruption.”

Our study shows, for the first time, that reducing the dose or intensity of treatment is a feasible option and produces similar outcomes as standard dose treatments for intermediate-fit patients.
— Alessandra Larocca, MD, PhD

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In fact, long-term use of dexamethasone-based regimens have been associated with insomnia, anxiety, agitation, weight gain, and edema. Finding ways to adapt treatments for older patients and those with functional deficits to allow them to remain on treatment longer and maintain disease control is critically important. As such, researchers wanted to evaluate whether stopping dexamethasone early, after initial therapy, and tapering the dose of lenalidomide (to 10 mg/d) would still benefit older intermediate-fit patients with newly diagnosed multiple myeloma who were not eligible for transplantation.

Methods and Findings

A total of 199 patients were enrolled and randomly assigned to one of two study groups between October 2014 and October 2017. Only individuals deemed to be intermediately fit were eligible for the study; patients were excluded if they were considered to be either fit or frail based on the International Myeloma Working Group frailty scale. Of these participants, 98 were randomly assigned to receive continuous Rd, and 101 received the adjusted dose and schedule after nine Rd induction cycles.

After a median follow-up of 37 months, those who were no longer taking dexamethasone experienced a significantly longer period without an adverse event or relapse compared with those who continued on the standard Rd therapy (event-free survival of 10.4 months vs 6.9 months, respectively). The tailored approach was also better tolerated, resulting in fewer adverse effects. Of the adverse events observed on the tailored approach, most were minor, including low white blood cell counts, infections, and skin disorders. The groups showed similar response rates, as well as similar chances of staying free of disease progression.

The findings could have important implications for practice. Dr. Larocca estimated that about one-third of patients with myeloma not eligible for stem cell transplantation fit the criteria used in this study.

“We expect the results of this study may help to improve and optimize the treatment of elderly patients who may be at greater risk of treatment toxicity and poor survival due to their age or comorbidities,” she said, adding that ongoing trials are now evaluating steroid sparing in combination with monoclonal antibodies, as well as the role of frailty-guided treatment.

Disclosure: For full disclosures of the study authors, visit ashpublications.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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