Sustained bone marrow and imaging MRD negativity for 3 years drives discontinuation of maintenance post ASCT in myeloma

• The treatment-free survival rate at 36 months post lenalidomide maintenance discontinuation was 75.8% (95%CI: 64%-90%).

• Out of the 12 patients who reversed from MRD negative to MRD positive and restarted maintenance, 4 progressed and all remain alive.

Discontinuation of lenalidomide maintenance post autologous transplantation (ASCT) is a burning question within the myeloma (MM) community, especially after the inclusion of MRD in the disease response criteria. In this prospective study, we evaluated the conversion to MRD positivity, the treatment-free survival (TFS) and the progression-free survival (PFS) in 52 MM patients, who discontinued lenalidomide maintenance, after achievement of sustained bone marrow and imaging MRD negativity for three years. Patients who developed MRD positivity after lenalidomide discontinuation, restarted lenalidomide maintenance at the same dose. The median follow-up from lenalidomide discontinuation was 3 years. Overall, 12 (23%) patients obtained MRD positivity and restarted lenalidomide maintenance. Only four (7.6%) patients progressed; 3 had a biochemical progression and one had a clinical progression. The overall median PFS was not reached, while the 7-year PFS from diagnosis was 90.2%. The 1-, 2- and 3-year TFS rates were 93.9%, 91.6% and 75.8%, respectively, whereas the 1-, 2- and 3-year landmark PFS rates from maintenance discontinuation (study entrance) were 96.0%, 96.0% and 92.9%, respectively. There were no statistically significant associations between age, gender, R2-ISS, type of induction therapy and use of consolidation therapy and the effect outcomes of PFS, TFS. We conclude that MRD discontinuation after 3-year sustained marrow and imaging MRD negativity is associated with low rates of MRD conversion and progressive disease. Thus, in the era of modern anti-myeloma treatments, a subgroup of patients may remain treatment free while in complete remission, without jeopardizing disease response.