A panel of leading multiple myeloma experts convened to discuss updates in maintenance therapy approaches, focusing on treatment combinations and bone-modifying strategies according to the latest NCCN guidelines. The discussion, led by Beth Faiman, CNP, PhD, from Cleveland Clinic, brought together specialists from major cancer centers across the United States.
Evolving Landscape of Maintenance Therapy
The NCCN guidelines currently recommend lenalidomide as the category 1 preferred regimen for maintenance therapy in transplant-eligible patients. However, emerging data suggests potential benefits from combination approaches, including daratumumab plus lenalidomide or carfilzomib plus lenalidomide.
Dr. Larry Anderson highlighted the importance of risk stratification, noting that treatment decisions are influenced by "patient's risk factors, their chromosomes, and their response." For high-risk patients, extended treatment with daratumumab plus lenalidomide may be considered, particularly if they haven't achieved MRD negativity.
The phase 3 PERSEUS trial has significantly influenced current practice, with many institutions now implementing extended post-transplant treatment using daratumumab-based combinations. Dr. Hans Lee suggested that daratumumab plus lenalidomide will likely become the standard of care, particularly for MRD-positive patients after consolidation.
MRD Monitoring and Treatment Duration
The PERSEUS trial revealed impressive MRD negativity rates, with the D-VRd arm showing 63.9% negativity at the 10^-5 threshold up to 36 months, compared to 30.8% in the VRd arm. These results are particularly significant for high-risk patients, as noted by Dr. Anderson, who observed benefits even in patients with two or more high-risk cytogenetic abnormalities.
Dr. Lee described using MRD status to guide treatment decisions, particularly in older patients with standard-risk disease. "If a patient is in their 70s with standard-risk multiple myeloma and had already attained MRD negativity, then I do have some patients who opt to collect stem cells but defer transplant after discussion of risks and benefits," he explained.
Bone-Modifying Therapy Approaches
The panel emphasized the importance of supportive care through bone-modifying therapy. Dr. Cristina Gasparetto outlined a tiered approach:
- Zoledronic acid as first-line treatment for a minimum of 3 months
- Pamidronic acid consideration for older patients
- Denosumab for patients with renal insufficiency
Dr. Nooka emphasized cost considerations, noting that zoledronic acid is significantly more affordable than denosumab. He also stressed the importance of careful discontinuation protocols, particularly with denosumab, to prevent rebound osteoplastic activity.
Future Directions
The experts concluded by highlighting several key points:
- Treatment approaches must be individualized
- Quality of life considerations are paramount
- Ongoing trials investigating maintenance therapy cessation in MRD-negative patients show promising early results
- Future developments in CAR-T and bispecific antibodies may further transform the treatment landscape
Dr. Grajales-Cruz summarized the consensus, stating that "treatment for multiple myeloma is not a one-size-fits-all approach," emphasizing the need to balance optimal response with patient quality of life.
