PB2188 ANALYSIS OF MINIMAL RESIDUAL DISEASE IN PATIENTS WITH MULTIPLE MYELOMA RECEIVING DARATUMUMAB

Abstract

Background:Over the past two decades, with the advent of new drugs, the tactics of treatment of patients with multiple myeloma (MM) has changed significantly; however, the general problem of the effectiveness of MM therapy remains unresolved to date. This disease is characterized by a progressive course and development of resistance to both proteasome inhibitors (bortezomib) and immunomodulatory drugs (lenalidomide), i.e. double refractoriness. Anti‐CD38 monoclonal antibodies are suggested for the treatment of heavily‐pretreated patients, including patients with double refractoriness.Aims:To study the dynamics of minimal residual disease (MRD) in patients with MM with double refractoriness receiving daratumumab.MethodsSeven patients with MM refractory to prior bortezomib and lenalidomide treatment were included in the study from 2017 to 2019. The number of lines of previous therapy was 5 (median = 3). The average age of patients–61 years (48–76 years). Daratumumab was administered to all patients as an intravenous infusion at a dose of 16 mg/kg: weekly at Weeks 1‐8, biweekly at Weeks 9‐24 and from Week 25 till progression. MRD assessment in bone marrow aspirate using multicolor flow cytometry (with a sensitivity of 10−5) was performed every 3 months from the start of treatment. To assess the effectiveness of treatment, generally accepted criteria were used.Results:Overall response was 86%. Fifty‐seven % of patients achieved a very good partial response, 29% had a partial response and 14% developed disease progression during therapy. After 3 months of therapy, 6 (86%) patients were MRD‐positive (median 0.072%, range 0.017–0.15%), of these, in 5 patients the monitoring showed a decrease in the number of myeloma cells, while in one patient MRD‐negativity was achieved. One patient (14%) with a very good partial response, after 3 months from the start of therapy, achieved an indicator of MRD‐negativity <0.01% (median ‐ 0.005%), however, after 6 months the MRD status changed to positive.Summary/Conclusion:Daratumumab treatment regimen demonstrated a high level of general response. The MRD score reflects the clearance of residual tumor cells and is an important independent prognostic criterion for determining the depth of remission, for stratification by risk groups and disease prognosis.