FORTE trial: Impact of minimal residual disease on multiple myeloma patients
Dr Stefania Oliva – GIMEMA, European Myeloma Network, Italy
The FORTE trial is a phase II randomised trial enroling patients with newly diagnosed multiple myeloma, transplant eligible and younger than 65 years. Patients basically were randomised to receive three different treatment arms. Arm 1 included patients receiving KCd induction, carfilzomib cyclophosphamide dexamethasone followed by transplantation and another four cycles of KCd consolidation. Arm 2 included patients receiving KRd induction, carfilzomib lenalidomide and dexamethasone followed by transplantation and KRd consolidation. Finally, Arm 3 included patients receiving twelve cycles of KRd continuous treatment without transplantation. And then patients were randomised to receive maintenance with lenalidomide or carfilzomib plus lenalidomide.
What were the main aims of the study?
The main endpoint for this study was the evaluation of minimal residual disease. In particular we studied MRD by flow cytometry and in a correlative study we evaluated MRD by next generation sequencing. The main objective was to compare the two different techniques.
What were the key results?
Regarding results, basically we confirmed that there is a good clinical concordance between flow cytometry and next generation sequencing since clinical results were comparable. In particular we observed that patients who were MRD negative at pre-maintenance by flow had significant superior progression free survival and overall survival compared with patients who were positive with a hazard ratio of 0.36, 0.34, both by flow and NGS. Then we also evaluated the role of sustained MRD negativity, it means patients who had these two MRD negative samples at least one year apart, and we observed that both techniques highlight a very favourable prognostic group with multiple myeloma, with more than 90% of patients who are alive and did not progress at four years.
How can these results impact the future of research and treatment of multiple myeloma?
I think that our results can confirm that both techniques are useful to evaluate MRD and in particular that MRD is an important endpoint in clinical practice to evaluate different kinds of treatment regardless of PFS and overall survival and can be used as a surrogate for survival.
How is MRD important when considering the treatment of multiple myeloma?
MRD is the most important prognostic factor that can overcome standard prognostic factors such as FISH or International Staging System, a more revised International Revised Staging System. It means that even patients with high risk, when achieving MRD negativity, can have a good outcome because the achievement of MRD negativity overcomes the poor prognostic impact of this tool.
Is there anything you’d like to add?
Another important issue is that maintenance therapy can improve the MRD negativity rate. In particular in our study we showed that two drugs, carfilzomib and lenalidomide, can convert patients with MRD positivity before maintenance to MRD negativity significantly higher than lenalidomide alone, so I think that we should include maintenance as a strategy to improve MRD negativity.