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

Discontinuation of lenalidomide maintenance after autologous stem cell transplantation is a burning question within the multiple myeloma (MM) community, especially after the inclusion of minimal residual disease (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 patients with MM who discontinued lenalidomide maintenance after achieving sustained bone marrow and imaging MRD negativity for 3 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 4 (7.6%) patients progressed; 3 had a biochemical progression and 1 had a clinical progression. The overall median PFS was not reached, whereas 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 among age, sex, Second Revision International Staging System, type of induction therapy, and use of consolidation therapy and the effect outcomes of PFS and TFS. We conclude that maintenance discontinuation after 3 years of sustained marrow and imaging MRD negativity is associated with low rates of MRD conversion and progressive disease. Thus, in the era of modern antimyeloma treatments, a subgroup of patients may remain treatment free while in complete remission without jeopardizing disease response.