PERSEUS Trial: Progression-Free Survival
Panelists discuss recent data showing that sustained minimal residual disease (MRD) negativity strongly predicts long-term progression-free survival (PFS) in multiple myeloma, regardless of whether patients receive a 4-drug daratumumab-based regimen or standard-drug therapy, emphasizing MRD negativity as a key surrogate end point; they also highlight challenges in predicting who benefits most from intensive therapy and the importance of individualized dosing strategies to balance efficacy and tolerability across different patient populations.
EP: 1.Introduction/Treatment Overview of Transplant-Ineligible Newly Diagnosed Multiple Myeloma
EP: 2.CEPHEUS Trial: Design/Baseline Characteristics
EP: 3.CEPHEUS Trial: MRD Negativity
EP: 4.CEPHEUS Trial: Efficacy in Transplant-Ineligible Patients
EP: 5.CEPHEUS Trial: Adverse Events
EP: 6.Treatment Overview of Transplant-Eligible Newly Diagnosed Multiple Myeloma
EP: 7.PERSEUS Trial: Design/Baseline Characteristics
EP: 8.PERSEUS Trial: MRD Negativity
EP: 9.PERSEUS Trial: Progression-Free Survival
EP: 10.PERSEUS Trial: Adverse Events
EP: 11.Key Takeaways/Final Comments
Recent data highlight the strong prognostic value of sustained MRD negativity in multiple myeloma, regardless of whether patients received a 4-drug regimen including daratumumab (Dara-VRD) or the standard 3-drug VRD. Patients achieving sustained MRD negativity showed remarkably high PFS rates of about 94% to 95% at 4 years, meaning only about 1 in 20 experienced disease progression. Those who did not achieve sustained MRD negativity had lower but still favorable outcomes, underscoring that deep and durable responses remain a critical end point beyond initial overall response rates. This growing recognition suggests that sustained MRD negativity is a powerful surrogate marker for long-term patient outcomes.
The data also bring attention to current clinical challenges, including the lack of reliable tools to predict which patients require the more intensive 4-drug regimen up front. While it is hoped that molecular profiling or other baseline characteristics may guide personalized therapy in the future, at present the 4-drug approach is broadly favored due to its ability to increase the likelihood of sustained MRD negativity with manageable added toxicity. Some experts believe that higher sensitivity testing (down to 10^-7) may reveal further differences in depth of response achievable with the 4-drug regimen, reinforcing its potential advantages.
When considering administration, dosing strategies differ somewhat between transplant-eligible and older patients. In transplant-eligible patients, maintaining dose intensity—such as lenalidomide at 25 mg and possibly twice-weekly bortezomib—is often pursued to achieve rapid deep responses, facilitating timely stem cell collection and transplant. However, dosing is individualized to balance efficacy with toxicity, particularly peripheral neuropathy risk. This nuanced approach reflects the broader principle that treatment regimens must be tailored to patient-specific factors rather than a one-size-fits-all model.
