Treatment Discontinuation After Achieving MRD Negativity in Multiple Myeloma in the Pre-BCMA Era: A Prospective,...

Minimal/measurable residual disease (MRD) negativity in multiple myeloma (MM) is associated with favourable outcomes; nonetheless, evidence supporting treatment discontinuation remains limited. We evaluated the feasibility of discontinuing antimyeloma therapy in patients with MRD negativity.

We analysed 41 patients who discontinued therapy after achieving MRD negativity at the 10^-5 level in the bone marrow (BM) and on imaging studies. Treatment regimens and lines of therapy were not prespecified. After discontinuation, patients were monitored with periodic MRD assessments. Salvage therapy was initiated at disease progression. For isolated BM-MRD conversion, treatment decisions were made jointly by the investigator and the patient.

The 2- and 3-year treatment-free survival (TFS) rates were 71.2% (95% CI, 54.0-83.0) and 67.9% (95% CI, 50.1-80.4), respectively, with the median not reached. Among the 34 patients with > 2 years of follow-up, 19 (55.9%) maintained MRD negativity at 2 years. High-risk cytogenetic abnormalities were associated with shorter TFS, whereas a BM normal plasma cell proportion ≥ 0.003% at discontinuation was associated with prolonged TFS.

Treatment discontinuation may be feasible in selected patients with MM who achieve and sustain MRD negativity, particularly in those without high-risk cytogenetics or with normal plasma cell recovery in the BM. Trial Registration: The authors have confirmed clinical trial registration is not needed for this submission.