After staying negative for measurable residual disease (MRD) for three years while getting lenalidomide maintenance, patients with multiple myeloma (MM) who discontinued the therapy mostly remained MRD negative and free of progressive disease after three years, researchers reported.
The encouraging results, published in Blood, raise the prospect of more patients being able to stop lenalidomide therapy with little worry that doing so will worsen their disease outlook, although the authors highlighted the relatively short time horizon of the study and the small group, with just 52 patients.
“Our study suggests that a subpopulation of patients who remain in deep marrow and imaging remission — MRD negative according to International Myeloma Working Group criteria of response — could discontinue treatment without impairing their disease status,” said lead author Evangelos Terpos, MD, PhD, director of the stem cell transplantation unit at Alexandra General Hospital in Greece and professor of hematology at the University of Athens.
The current practice is to give lenalidomide maintenance until disease progression, and there is not much literature to suggest how long patients should stay on the drug. Some patients discontinue lenalidomide at their physician’s discretion due to toxicity concerns and then stay in close follow-up while they remain in remission. The new findings, though, suggest that freedom from therapy could be an option in even more cases.
In the study, researchers tracked patients with MM who had received four to six cycles of a triplet or quadruplet induction therapy, followed by high-dose melphalan, autologous hematopoietic cell transplant (AHCT), and at least three years of lenalidomide maintenance. Those who had sustained bone marrow MRD negativity for three years — evaluated every year — and MRD negativity on imaging were eligible for the study.
If a patient who had discontinued lenalidomide maintenance then became MRD positive, treatment was resumed. Patients were started on a second-line treatment if they developed progressive disease.
Of 194 patients followed from 2016 to 2021, 52 met the criteria and were enrolled. They were a median of 56.5 years old (range = 39-66). Thirty-two patients had stage 1 disease according to the Revised International Staging System; 17 had stage 2 disease; and three had stage 3 disease. Eleven patients had MM with at least one high-risk cytogenetic abnormality.
All of the patients had received bortezomib-based induction regimens with a median of four induction cycles. When lenalidomide maintenance was started, all 52 patients had achieved at least a very good partial response, and eight were bone marrow MRD positive, while 44 were already bone marrow MRD negative.
Once patients entered the study and lenalidomide was discontinued, 12 of the 52 patients became MRD positive and restarted lenalidomide. At 12, 24, and 48 months, the percentages of patients who became MRD-positive were 7.7%, 13.5%, and 23%, respectively.
Half of the patients who converted to MRD positivity had MM with at least one high-risk cytogenetic abnormality, researchers reported. No one developed progressive disease before they were found to have converted to MRD positivity.
From the restarting of lenalidomide, the median follow-up time was 11.5 months. Four patients had progressive disease in the three-year total follow-up period of the study, researchers reported — two with MM with high-risk cytogenetics and two with standard-risk disease. All four of these patients received anti-CD38 triplet therapy, and three are in remission, while the fourth progressed and received third-line treatment.
Of the other eight patients who became MRD positive, all restarted lenalidomide maintenance and are in remission. Seven are still MRD positive, and one again became MRD negative after six months of being retreated with lenalidomide.
Dr. Terpos said lenalidomide discontinuation could be considered on a broader basis, although validation in a larger cohort and, preferably, in a randomized trial is needed.
“Our study suggests that around 25% of patients could achieve sustained MRD negativity post-AHCT, and thus long-term disease control,” he said. “For this subgroup, lenalidomide discontinuation and close assessment of MRD might be considered.”
But, he added, “Physicians should carefully evaluate the depth of the response of a patient in longitudinal assessments before considering maintenance discontinuation. Moreover, the patient should be thoroughly informed before deciding on lenalidomide discontinuation.”
Any conflicts of interest declared by the authors can be found in the original article.
Reference
Terpos E, Malandrakis P, Ntanasis-Stathopoulos I, et al. Sustained bone marrow and imaging MRD negativity for 3 years drives discontinuation of maintenance post ASCT in myeloma [published online ahead of print, 2025 Feb. 26]. Blood. doi: 10.1182/blood.2024027686.
