Dr Baljevic on the PERSEUS Trial in Untreated Multiple Myeloma

Muhamed Baljevic, MD, FACP, hematologist, medical oncologist, associate professor, medicine, Division of Hematology Oncology, director, Plasma Cell Disorders Research, director, Vanderbilt Amyloidosis Multidisciplinary Program, Vanderbilt-Ingram Cancer Center; co-chair, the Vanderbilt-Ingram Cancer Center Protocol Review and Monitoring System, discusses the phase 3 PERSEUS trial (NCT03710603) in patients with previously untreated multiple myeloma.

The PERSEUS trial examined daratumumab (Darzalex) followed by autologous stem cell transplant (ASCT) and daratumumab, bortezomib (Velcade), lenalidomide (Revlimid), and dexamethasone (D-VRd), Baljevic begins. A unique aspect of the PERSEUS trial design was that patients who achieved sustained minimal residual disease (MRD) negativity for 12 months, following at least 2 years of maintenance with daratumumab, were allowed to discontinue daratumumab and continue with lenalidomide alone, he reports. If these patients lost their MRD-negative status or complete response, they had the option to restart daratumumab. This feature of the trial is particularly significant because it reflects the current trend toward developing more refined and potentially less intensive treatment strategies, Baljevic states.

An important takeaway regarding quadruplet therapies, which are the standard of care in North America for patients with treatment-naive multiple myeloma, is their limited global accessibility due to high costs, according to Baljevic. Although costs are a crucial consideration, the PERSEUS trial still demonstrated positive efficacy outcomes, showing a comparative PFS benefit with the quadruplet therapy over triplet therapy with VRd induction and consolidation followed by maintenance with lenalidomide alone after a median follow-up of 47.5 months, Baljevic explains.

Another valuable aspect of the PERSEUS trial is the data on sustained MRD negativity after at least 12 months, he continues. These data are significant as they align with the FDA’s Oncologic Drugs Advisory Committee's emphasis on MRD as a crucial end point in multiple myeloma, Baljevic notes. The trial revealed that approximately 64% of patients in the D-VRd group discontinued daratumumab after achieving sustained MRD negativity, highlighting the potential for de-escalating treatment, Baljevic says.

This trial provides critical data to guide clinical decisions, Baljevic emphasizes. It raises essential questions about when and to what extent oncologists can safely reduce therapy in patients with multiple myeloma, he explains. Understanding when to de-escalate therapy, the appropriate steps for maintenance, and the circumstances under which therapy should be resumed are all vital considerations, Baljevic concludes.