Prolonged Lenalidomide Maintenance Deepens Disease Response in MM

Long-term use of lenalidomide as a maintenance therapy in patients with multiple myeloma (MM) can increase the depth of response and improve overall outcomes, according to new research.

Lenalidomide has been found to boost progression-free survival when administered following induction therapy, but until now the impacts of prolonged use on minimal residual disease (MRD) kinetics and survival had not been studied in depth.

In a new study published in the journal Blood Advances, a team of investigators from the Spain and the United States retrospectively analyzed 139 patients who received lenalidomide in a real-world clinical setting and whose MRD levels were tracked by multiparametric flow cytometry or next-generation sequencing with a sensitivity of at least 10^-4. The authors found that treatment with lenalidomide was linked with an increased depth of disease response.

Specifically, 38.1% of patients achieved maximum response during maintenance, and 34.3% of patients who entered maintenance therapy MRD-positive achieved MRD-negative status during maintenance therapy. Further analysis showed patients who had progressively decreasing MRD levels also had better progression-free survival (PFS) compared to those whose MRD levels were not decreasing during maintenance.

Coauthor Rafael Alonso Fernández, MD, of Complutense University of Madrid, in Spain, told The American Journal of Managed Care^® his team was struck by the impact of the therapy, noting that they found patients whose MRD levels were decreasing obtained a survival benefit even if they never made it to MRD negativity.

“In fact, in our study, with all the inherent limitations, these patients did not show differences in PFS outcomes compared with those who eventually obtained MRD-negative,” he added.

This suggests that it might make sense for physicians to track patients’ progress using serial MRD assessments during maintenance, he said.

More broadly, Alonso said the study offers confirmation that lenalidomide deepens disease response in many patients in such a way as to boost survival.

In the study, Alonso and colleagues note that it took a long time for regulators to widely approve lenalidomide as a maintenance therapy. He said that could be due to a number of factors, including some concern that it might increase the risk of secondary primary neoplasms.

However, Alonso said the end result of that lengthy regulatory process was that regulators were able to glean a better understanding of the balance of risks and benefits of lenalidomide maintenance therapy, which in turn can better inform clinician’s decisions.

Asked if these findings would affect therapy for patients who are MRD-negative following induction therapy, Alonso said it would be difficult to draw broad conclusions from this study. However, he noted that they found a 26% relapse rate among subgroups that achieved MRD-negative status either during induction or maintenance therapy.

“Accordingly, it seems reasonable to think that these patients are not exempt from risk and they could also obtain some benefit from the maintenance treatment,” he said.

Alonso said he hopes further study helps provide additional information, such as whether it might be appropriate to suspend maintenance treatment if certain criteria are met. He said further analysis using a higher sensitivity for MRD will also be important to allow more for detailed decision-making.

Reference

Alonso R, Cedena MT, Wong S, et al. Prolonged lenalidomide maintenance therapy improves the depth of response in multiple myeloma. Blood Adv. 2020;4(10):2163‐2171. doi:10.1182/bloodadvances.2020001508