Minimal Residual Disease in Multiple Myeloma: Surrogate Biomarker for Trial Evaluation?
Minimal residual disease (MRD) of less than 1 tumor cell in 1 million bone marrow cells—MRD 10-6—is a potential “novel surrogate biomarker for trial evaluation,” according to Hervé Avet-Loiseau, MD, PhD, of IUC-Oncopole, Unite de Genomique du Myelome, Toulouse, France. He led a research team in the prospective IMF2009 trial. The results, said Dr. Avet-Loiseau in a presentation at the 2017 American Society of Hematology (ASH) Annual Meeting & Exposition (Abstract 435), suggest “that 10-6 should be the optimal cutoff.”
In the trial, 700 patients with multiple myeloma received lenalidomide, bortezomib, and dexamethasone induction and then were randomized to receive or not receive transplantation conditioned by high-dose melphalan. All patients had 12 months of lenalidomide maintenance. Post treatment, 269 of the 700 patients had at least a very good partial response (the rest were considered MRD-positive).
Of the patients with a very good partial response, those found to be MRD-negative with immunoglobulin gene next-generation sequencing, with the MRD 10-6 standard, had better outcomes:
- At a median follow-up of 55 months, median progression-free survival for MRD-negative patients had not been reached; it was 29 months for those who had not achieved MRD negativity.
- Whether they did or did not receive transplantation, patients who achieved MRD negativity had similar outcomes.
- Patients considered high-risk by cytogenetics who achieved MRD negativity had significantly better outcomes than standard-risk patients who did not achieve it.
- Patients who achieved MRD negativity had significantly longer overall survival rates.