Persistent bone marrow minimal residual disease as a “high‐risk” disease feature in multiple myeloma

Mohan, Meera; Szabó, Anikó; Yarlagadda, Naveen; Gundarlapalli, Sravani; Thanendrarajan, Sharmilan; Kendrick, Samantha; Schinke, Carolina; Alapat, Daisy; Sawyer, Jeffrey R.; Tian, Erming; Tricot, Guido; Rhee, Frits van; Zangari, Maurizio

doi:10.1002/ajh.26255

Cited by 5 publications

(6 citation statements)

References 20 publications

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“…More importantly, we show that MRD conversion from negative to positive confers a more favorable outcome compared with patient with persistent MRD positivity throughout the disease course. 31,32 In a subset of patients with serial MRD assessment from diagnosis, we noted an apparent paradox of early attainment of MRD negativity associated with an inferior clinical outcome. This is in agreement with previous publications showing that a precipitous response to induction therapy is an indicator of a more proliferative MM.…”

Section: Discussionmentioning

confidence: 73%

Clinical implications of loss of bone marrow minimal residual disease negativity in multiple myeloma

et al. 2022

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Multiple myeloma (MM) patients frequently attain a bone marrow (BM) minimal residual disease (MRD) negativity status in response to treatment. We identified 568 patients who achieved BM MRD negativity following autologous stem cell transplantation (ASCT) and maintenance combination therapy with an immunomodulatory agent and a proteasome inhibitor. BM MRD was evaluated by next generation flow cytometry (sensitivity of 10-5 cells) at 3 to 6 months intervals. With a median follow up of 9.9 years from diagnosis (range, 0.4 - 30.9), 61% of patients maintained MRD negativity, while 39% experienced MRD conversion at a median of 6.3 years (range, 1.4 - 25). The highest risk of MRD conversion occurred within the first 5 years after treatment and was observed more often in patients with abnormal metaphase cytogenetic abnormalities (95%vs. 84%; P = 0.001). MRD conversion was associated with a high risk of relapse and preceded it by a median of 1.0 year (range, 0 - 4.9). However, 27% of MRD conversion positive patients had not yet experienced a clinical relapse with a median follow-up of 9.3 years (range, 2.2 - 21.2). Landmark analyses using time from ASCT revealed patients with MRD conversion during the first 3 years had an inferior overall and progression-free survival compared to patients with sustained MRD negativity. MRD conversion correctly predicted relapse in 70%, demonstrating the utility of serial BM MRD assessment to complement standard laboratory and imaging to make informed salvage therapy decisions.

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Section: Discussionmentioning

confidence: 73%

Clinical implications of loss of bone marrow minimal residual disease negativity in multiple myeloma

et al. 2022

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“…However, it is still unclear of how to reach this goal, e.g., in patients who failed to achieve MRD negativity during standard treatment. Mohan et al 34 recently confirmed that persistent MRD positivity despite change in treatment is associated with inferior clinical outcome. Intensifying therapy may be a way to address this issue as carfilzomib/lenalidomide maintenance resulted in a superior rate of MRD‐negative patients compared to lenalidomide monotherapy in the FORTE trial (http://clinicaltrials.gov Identifier: NCT02203643) 35 .…”

Section: Discussionmentioning

confidence: 95%

Minimal residual disease and imaging‐guided consolidation strategies in newly diagnosed and relapsed refractory multiple myeloma

et al. 2022

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Measurement of minimal residual disease (MRD) by next-generation flow cytometry (NGF) is an important tool to define deep responses in multiple myeloma (MM).However, little is known about the value of combining NGF with functional imaging and its role for MRD-based consolidation strategies in clinical routine. In the present study, we report our experience investigating these issues with 102 patients with newly diagnosed (n = 57) and relapsed/refractory MM (n = 45). Imaging was performed using either positron emission tomography or diffusion-weighted magnetic resonance imaging. In all, 45% of patients achieved MRD-negativity on both NGF and imaging (double-negativity), and 8% and 40% of patients were negative on either NGF or imaging respectively. Thus, in a minority of patients imaging was the only technique to detect residual disease. Imaging-positivity despite negativity on NGF was more common in heavily pretreated disease (four or more previous lines) compared to newly diagnosed MM (p < 0.01). Among the 29 patients undergoing MRD-triggered consolidation, 51% responded with MRD conversion and 21% with improved serological response. MRD-triggered consolidation led to superior progression-free survival (PFS) when compared to standard treatment (p = 0.04). In conclusion, we show that combining NGF with imaging is helpful particularly in patients with heavily pretreated MM, and that MRD-based consolidation could lead to improved PFS.

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“…4,15 MRD positivity particularly confers poor outcome in the setting of HR disease. 3,16 Our study population is enriched in HR disease (63%) with BM MRD positivity in all patients after ASCT1. Overall, there was augmentation of disease responses including attainment of MRD negativity in about 50% of patients after ASCT2 that translated into improved PFS.…”

Section: Tandem Autologous Stem Cell Transplantation In Patients With...mentioning

confidence: 99%

“…BM aspirate MRD assessment was performed using clinically validated 8-color flow cytometric analysis with a minimal sensitivity of 10 À5 cells 12,13 and was performed within 100 days of ASCT1 and ASCT2. 3 The median age at ASCT1 was 58 (interquartile range [IQR] 52-63) yrs with 40% (68/168) being female patients (Table S1). Black patients accounted for 16% (n = 26) of all patients.…”

Section: Tandem Autologous Stem Cell Transplantation In Patients With...mentioning

confidence: 99%

Tandem autologous stem cell transplantation in patients with persistent bone marrow minimal residual disease after first transplantation in multiple myeloma

et al. 2022

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Persistent bone marrow minimal residual disease as a “high‐risk” disease feature in multiple myeloma

Abstract: curves: (A) shows the relapse free survival and (B) overall survival of persistent MRD positivity compared to those with sustained MRD negativity. (C) shows relapse free and ID overall survival when patients were stratified based on GEP70 score (HR vs. LR) CORRESPONDENCE

Cited by 5 publications

References 20 publications

Clinical implications of loss of bone marrow minimal residual disease negativity in multiple myeloma

Clinical implications of loss of bone marrow minimal residual disease negativity in multiple myeloma

Minimal residual disease and imaging‐guided consolidation strategies in newly diagnosed and relapsed refractory multiple myeloma

Tandem autologous stem cell transplantation in patients with persistent bone marrow minimal residual disease after first transplantation in multiple myeloma

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