Danish real-world data study drives Medicines Council to reassess multiple myeloma treatment

The Danish Medicines Council (Medicinrådet) will reassess lenalidomide’s use in multiple myeloma treatment after real-world evidence (RWE) showed reduced effectiveness.

The Danish Medicines Council is set to reassess its recommendation for the drug lenalidomide (Revlimid), available as a maintenance treatment for multiple myeloma, after a Danish real-world study revealed its effectiveness to be significantly less than expected. The decision, made during a recent council meeting, marks a critical juncture in the evaluation of treatment protocols for multiple myeloma.

In 2019, the Danish Medicines Council recommended lenalidomide as a maintenance therapy for patients with multiple myeloma following high-dose chemotherapy and stem cell support. This recommendation was based on clinical trial data suggesting that the drug could prolong progression-free survival by almost 2 years. However, the new Danish study, published in the eJHaem in April 2024, paints a different picture. It shows that the introduction of lenalidomide as a nationwide treatment option in Denmark did not lead to the expected clinical outcomes.

The nationwide availability of lenalidomide across all regions provided a unique opportunity to study its real-world usage, effectiveness, and adverse effects in a broad, population-based cohort without referral bias. The study included nearly 300 people with newly diagnosed multiple myeloma who received lenalidomide between June 2019 and March 2022. It found no significant improvement in overall survival or progression-free survival, with over half of the patients discontinuing treatment due to side effects. The authors note:

“A major strength of our study is the natural experiment resulting from a nationwide and simultaneous introduction of LM [lenalidomide]. We take advantage of the randomness in being diagnosed and treated with HDM‐ASCT just before or just after June 2019, which effectively eliminates confounding by indication…. Our results are surprising, but we do caution interpretation. We show that the clinical outcomes of patients with MM [multiple myeloma] in Denmark treated with [high‐dose melphalan and autologous stem cell transplantation] HDM‐ASCT have not improved since the introduction of LM. Whether this observation is explained by residual confounding, or that improved induction and relapse treatment has diminished the effect of LM, cannot be established with certainty based on our results.”

---

Implications for the Danish Medicines Council

The results from the real-world study have prompted the Danish Medicines Council to reconsider its stance. “Even though we also had many discussions about this particular treatment at the time of the recommendation, it is still surprising that the Danish real-world study shows such little effect,” said Jørgen Schøler Kristensen, head of the Medical Council. He added, “We have to look at the overall picture again to ensure that our recommendations align with reality and that patients receive the treatments that benefit them the most.”

Kristensen highlighted the significance of RWE in the council’s decision-making process. While acknowledging that “real-world evidence is weaker evidence than we get from well-conducted randomized clinical trials,” he stressed the importance of reassessing treatments when new evidence emerges that deviates from the original data. The council plans to inform the Danish Medicines Agency of the findings, as the agency monitors medication side effects in Denmark.

---

RWE for treatment evaluations

The reassessment of lenalidomide could set a precedent for future evaluations of medical treatments based on real-world data. Kristensen has a “clear ambition” to follow up on all national recommendations made by the council, particularly as more drugs are approved based on progression-free survival data alone. “This sharpens the need to ensure that the treatments have the expected effect when they reach the patients in the clinic,” he noted.

A final decision on the recommendation for lenalidomide is expected later this year. As Neil Grubert observed, “RWE has triggered a reassessment of a drug by the Danish Medicines Council for the first time,” underscoring the potential impact this decision could have on future healthcare practices.