PERSEUS Trial: Adverse Events
Panelists discuss that Dara-VRD offers significant benefits in sustained minimal residual disease (MRD) negativity and progression-free survival with a manageable safety profile, emphasizing dose adjustments and supportive care to balance efficacy and toxicity in frontline multiple myeloma treatment.
When treating patients with a high disease burden, clinicians may start bortezomib twice weekly to achieve a rapid response, then quickly reduce to once weekly to lower the risk of peripheral neuropathy. The safety profile of the 4-drug daratumumab plus VRD (Dara-VRD) regimen, as seen in the Perseus study, aligns closely with that of the 3-drug VRD regimen, showing no unexpected safety concerns. There is a slightly increased risk of neutropenia and infections, particularly pneumonia, but these adverse events are manageable and consistent with previous studies such as Cepheus.
To address neutropenia, growth factor support with granulocyte colony-stimulating factor is often effective alongside thoughtful dose adjustments. Lenalidomide dose reduction is typically the first modification when cytopenias arise. This careful management allows patients to continue therapy while minimizing toxicity, maintaining the balance between efficacy and safety. Overall, adverse events related to Dara-VRD are manageable, reinforcing its suitability for frontline use.
In summary, 2 pivotal trials comparing Dara-VRD with VRD in patients with newly diagnosed multiple myeloma have demonstrated significant improvements in sustained MRD negativity and progression-free survival. The Perseus study’s post-hoc analysis highlighted notable gains in sustained MRD negativity at 12 and 24 months with the 4-drug regimen. These findings, along with consistent safety data, further establish Dara-VRD as an important advancement in frontline myeloma treatment. Continued evaluation of emerging data will help refine patient selection and optimize treatment strategies for diverse patient populations.
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