Clinical Summary: 

• Design/Context: Long-term analysis of MRD dynamics from the phase 2 FORTE trial evaluating different induction, consolidation, and maintenance strategies in newly diagnosed multiple myeloma.
• Key Outcomes: Increasing duration of sustained MRD negativity was associated with progressively better long-term outcomes, with 3 years of sustained MRD negativity identifying a population with excellent survival and 5 years identifying patients with exceptionally low risk of progression.
• Clinical Relevance: Duration of MRD negativity may serve as a powerful prognostic marker and could help guide future treatment duration and risk-adapted management strategies in multiple myeloma.

Mattia D'Agostino, MD, University of Torino, Torino, Italy, discusses long-term measurable residual disease (MRD) analyses from the phase 2 FORTE trial in patients with multiple myeloma. 

Results demonstrate that longer durations of sustained MRD negativity are associated with progressively improved progression-free and overall survival, with exceptional outcomes observed after 3 to 5 years of sustained MRD negativity.

Dr D'Agostino presented these results at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois.

Transcript:

I'm Mattia D'Agostino, I'm from the University of Torino, and during ASCO 2026 we discussed the results of the long-term MRD dynamics within the FORTE trial.

We know that achieving MRD negativity in the bone marrow is maybe the single most powerful prognostic factor in multiple myeloma. However, we also know that sustained MRD negativity outperforms single time-point MRD negativity in predicting long-term PFS and OS. However, the optimal duration of sustained MRD negativity is still a matter of debate. 

Thus, we looked at long-term MRD outcomes in the phase 2 FORTE trial, which randomized patients to induction and consolidation with KRd plus transplant versus KRd alone versus KCd plus transplant. After consolidation, patients were randomized to KR doublet maintenance versus lenalidomide single agent. We focused on the maintenance part of the trial, where MRD was measured before maintenance and then every 6 months. We then tried to define sustained MRD negativity at 1 year, 2 years, 3 years, 4 years, or 5 years or more.

What we found is that longer MRD negativity duration progressively and consistently improved PFS prediction. Passing from MRD negativity lasting less than 1 year to MRD negativity lasting more than 5 years, the 7-year PFS rate increased from about 20% to 30% to more than 90%.

Moreover, if we focus on a population with at least 3 years of sustained MRD negativity, which was achieved in approximately 1/3 of patients, we can see that the long-term outcomes were very good, with a 7-year PFS rate of more than 80% and a 7-year overall survival rate of 97%. If you reach 3 years of sustained MRD negativity, then the outcome according to baseline risk factors, such as high-risk cytogenetics, doesn't seem to matter anymore. Thus, reaching 3 years of sustained MRD negativity is clinically very important.

Pushing our analysis to 5 years of sustained MRD negativity, we identified a population with exceptional long-term PFS, with 91% of patients remaining progression-free at 7 years. Moreover, at the last follow-up, only 6 patients had experienced disease progression, representing less than 10% of that population.

Source: 

D'Agostino M, Bertuglia G, Rota-Scalabrini D, et al. Impact of sustained MRD negativity for up to 5 years on long-term outcome of transplant-eligible newly diagnosed multiple myeloma patients enrolled in the randomized phase 2 FORTE trial. Presented at 2025 ASCO Annual Meeting. May 30 - June 3, 2025; Chicago, IL. Abstract 7504.