Stopping myeloma maintenance therapy at 2 years is safe, study shows
Halting treatment does not raise risk of progression or death
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Maintenance therapy for myeloma can be stopped after two years without raising the risk of disease progression or death, a new study shows.
“For years, patients and clinicians have been hesitant to stop lenalidomide maintenance because we didn’t know how long was required for optimal benefit,” Shaji Kumar, lead author of the study at Mayo Clinic, said in a press release. “Our trial results show that two years is sufficient and that continuing the drug longer adds toxicity without extending life.”
The study, “Continuous or Fixed-Duration Maintenance Therapy in Multiple Myeloma,” was published in The New England Journal of Medicine. The work was funded by the National Institutes of Health and Amgen.
Maintenance therapy raises thorny question
Myeloma is a form of blood cancer caused by the uncontrolled growth of immune cells in the bone marrow. In newly diagnosed patients, treatment of myeloma usually first involves induction therapy, where a combination of medications is administered, aiming to drive the cancer into remission.
Following induction treatment, the current standard of care is for patients to receive long-term maintenance therapy, where they continue to receive treatment in order to prevent the cancer from coming back. An immunomodulatory agent known as lenalidomide (sold as Revlimid and generics) is commonly used for maintenance therapy.
But the use of maintenance therapy has raised a thorny question: Should maintenance treatment be continued indefinitely, or can it be stopped eventually? On the one hand, continuing treatment with no end in sight can impose substantial burdens in the form of side effects and medical costs. But on the other hand, stopping treatment early might mean the cancer is more likely to come back. Until now, there’s been little data to guide clinicians in weighing these risks.
Outcomes generally comparable between two groups
To answer the question, scientists conducted a Phase 3 clinical trial called ENDURANCE (NCT01863550). The study enrolled more than 500 people with standard-risk newly diagnosed myeloma. All of the participants initially underwent standard induction therapy using lenalidomide in combination with a proteasome inhibitor and a corticosteroid. Then, all participants started maintenance therapy with lenalidomide.
In some patients, maintenance lenalidomide was continued indefinitely, but in others, maintenance was stopped after two years. The researchers then compared outcomes between the two groups over a median follow-up of more than seven years.
Results showed that outcomes were generally comparable between the two groups. At seven years, about two-thirds of patients in each group were still alive, and about one-third of patients had not experienced cancer progression. In fact, the only notable difference between the groups was that rates of side effects were higher in patients given indefinite maintenance treatment.
Our findings suggest that a fixed-duration approach can become the new standard of care, at least for standard-risk patients, allowing us to pause treatment, monitor patients closely, with the option of potentially re-introducing lenalidomide or other new active treatments if the disease returns.
Overall, these data suggest that maintenance therapy can be stopped after two years without increasing the risk of cancer recurrence or death.
“This phase 3 trial directly examined the question of duration of maintenance therapy in newly diagnosed multiple myeloma and showed that indefinite-duration maintenance with lenalidomide did not appear to have an overall survival benefit as compared with fixed-duration therapy (2 years),” the researchers concluded.
The researchers stressed that this study included a specific population of myeloma patients receiving a particular combination of induction and maintenance therapies, so it’s unclear how generalizable the results are.
“Our findings suggest that a fixed-duration approach can become the new standard of care, at least for standard-risk patients, allowing us to pause treatment, monitor patients closely, with the option of potentially re-introducing lenalidomide or other new active treatments if the disease returns,” said S. Vincent Rajkumar, MD, co-author of the study at Mayo Clinic.
The scientists noted that indefinite maintenance lenalidomide has been the long-term standard because initial clinical trials compared it against no maintenance at all. Since long-term therapy carries side effect risks as well as higher costs, the researchers emphasized a need for drug developers to proactively test the optimal length of therapy, not just whether any therapy is better than none.
“With a longer duration of therapy adding toxicity and cost, randomized trials to define appropriate durations of treatment must be done in parallel or shortly after new treatments are approved. It should not be assumed that a longer duration of therapy is likely to be better,” the scientists wrote.
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