P861: persistent bone marrow and imaging mrd negativity as criteria to stop lenalidomide maintenance following asct: preliminary results of a single-center prospective cohort study

Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: Autologous stem cell transplantation (ASCT) followed by lenalidomide maintenance is the standard of care for eligible patients with newly diagnosed multiple myeloma (MM). Sustained marrow and imaging minimal residual disease (MRD) correlate with prolonged progression-free survival (PFS) and overall survival (OS). Although they are often used as surrogate endpoints in clinical trials, it is not clear if they can drive clinical decisions. Many patients on lenalidomide maintenance will remain disease-free in the long-term. Aims: To define the optimal duration of maintenance with lenalidomide and determine criteria to discontinue maintenance safely. Methods: In this prospective study, we included patients with newly diagnosed MM from January 1st, 2016 to December 31st, 2019, who underwent ASCT followed by lenalidomide maintenance. MRD status was assessed in patients who had achieved stringent complete remission (sCR) and then at 6, 12, 24, and 36 months after the initiation of lenalidomide maintenance. MRD samples were evaluated by next generation flow, according to the EuroFlow protocol. Patients, who had at least 3 consecutive MRD negative results and had received at least 36 months of maintenance, underwent a PET/CT scan. If patients had achieved imaging MRD negativity, they discontinued lenalidomide maintenance and MRD was performed every 6 months thereafter. If a patient converted from MRD negative to positive or if the patient relapsed from sCR, lenalidomide maintenance was restarted. Results: Overall, 151 patients received induction with proteasome inhibitor-based regimens (VCD or VRD) and underwent ASCT. During a median follow-up of 70 months (range 6-84 months) from the time of ASCT, 44 (29.1%) patients had disease progression and 20 (13.2%) patients died. Out of 107 patients who did not progress or die, 42 (39.2%) patients achieved sustained bone marrow MRD negativity and imaging MRD negativity at 3 years after maintenance initiation. Thus, they discontinued lenalidomide maintenance, according to study schedule. Their median age at MM diagnosis was 56 years (range 43-66). Twenty-one (50%) patients were males, whereas 52.4% had IgG, 26.2% had IgA and 21.4% had light chain MM. The patient distribution per ISS was ISS 1 63.4%, ISS 2 19.5% and ISS 3 17.1%, whereas per R-ISS was RISS-1 57.5%, RISS-2 35% and RISS-3 7.5%. The median follow up time from maintenance discontinuation for all patients was 16 months (range 1-31). Six months after discontinuation of lenalidomide maintenance, 39 out of 41 patients were found to be MRD negative. At 12 months post-lenalidomide discontinuation, 36 out of 38 patients continued to be MRD negative. At 18 months, all evaluable patients (n=18) remained MRD negative. At 24 months, 13 out of 14 patients were MRD negative and at 30 months all 4 evaluable patients were MRD negative. Overall, five patients restarted treatment with lenalidomide monotherapy after converting from MRD negative to MRD positive following the initial completion of maintenance, and out of them one patient progressed and received second line of treatment. Only one patient who discontinued maintenance died for reasons not related to multiple myeloma, and with no symptoms of disease progression. Summary/Conclusion: We conclude that sustained MRD negativity after ASCT and a completion of 3 years lenalidomide maintenance may guide the safe discontinuation of maintenance, although this has to be proven in prospective randomized clinical trials. Close follow-up with consecutive MRD testing can trace an early myeloma relapse. Keywords: Minimal residual disease (MRD), Multiple myeloma, Flow cytometry, Maintenance