Abstract
BackgroundMultiple myeloma remains an incurable disease with multiple relapses due to residual myeloma cells in the bone marrow of patients after therapy. Presence of small number of cancer cells in the body after cancer treatment, called minimal residual disease, has been shown to be prognostic for progression-free and overall survival. However, for multiple myeloma, it is unclear whether patients attaining minimal residual disease negativity may be candidates for treatment discontinuation. We investigated, if longitudinal flow cytometry-based monitoring of minimal residual disease (flow-MRD) may predict disease progression earlier and with higher sensitivity compared to biochemical assessments.MethodsPatients from the Nordic countries with newly diagnosed multiple myeloma enrolled in the European-Myeloma-Network-02/Hovon-95 (EMN02/HO95) trial and undergoing bone marrow aspiration confirmation of complete response, were eligible for this Nordic Myeloma Study Group (NMSG) substudy. Longitdudinal flow-MRD assessment of bone marrow samples was performed to identify and enumerate residual malignant plasma cells until observed clinical progression.ResultsMinimal residual disease dynamics were compared to biochemically assessed changes in serum free light chain and M-component. Among 20 patients, reaching complete response or stringent complete response during the observation period, and with ≥3 sequential flow-MRD assessments analysed over time, increasing levels of minimal residual disease in the bone marrow were observed in six cases, preceding biochemically assessed disease and clinical progression by 5.5 months and 12.6 months (mean values), respectively. Mean malignant plasma cells doubling time for the six patients was 1.8 months (95% CI, 1.4–2.3 months). Minimal malignant plasma cells detection limit was 4 × 10–5.ConclusionsFlow-MRD is a sensitive method for longitudinal monitoring of minimal residual disease dynamics in multiple myeloma patients in complete response. Increasing minimal residual disease levels precedes biochemically assessed changes and is an early indicator of subsequent clinical progression.Trial registrationNCT01208766
Highlights
Multiple myeloma (MM) is a common malignant gammopathy and associated with a wide spectrum of symptoms [1]
Flow-MRD is a sensitive method for longitudinal monitoring of minimal residual disease dynamics in multiple myeloma patients in complete response
In 53 patients, a bone marrow (BM) aspirate sample was sent for a first response assessment by flow cytometry (1st flow-RA), when assumed to be in CR/Stringent CR (sCR) at any time during the course
Summary
Multiple myeloma (MM) is a common malignant gammopathy and associated with a wide spectrum of symptoms [1]. Patients typically present with proliferation of abnormal monoclonal plasma cells (PC) in the bone marrow (BM) and monoclonal protein (M-component) in the serum and/or urine [2]. Complete response is biochemically defined as non-detectable M-component in the serum and urine by immunofixation plus disappearance of any soft tissue plasmacytoma, and detection of < 5% plasma cells in BM. Multiple myeloma remains an incurable disease with multiple relapses due to residual myeloma cells in the bone marrow of patients after therapy. Presence of small number of cancer cells in the body after cancer treat‐ ment, called minimal residual disease, has been shown to be prognostic for progression-free and overall survival. For multiple myeloma, it is unclear whether patients attaining minimal residual disease negativity may be candidates for treatment discontinuation. If longitudinal flow cytometry-based monitoring of minimal residual disease (flow-MRD) may predict disease progression earlier and with higher sensitivity compared to biochemical assessments
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