Generic placeholder image

Reviews on Recent Clinical Trials

Editor-in-Chief

ISSN (Print): 1574-8871
ISSN (Online): 1876-1038

Research Article

Long-term CR Multiple Myeloma Patients Show Cured or MGUS-like Minimal Residual Disease Pattern by Next Generation Flow

Author(s): Alessandro Gozzetti*, Paola Pacelli, Donatella Raspadori, Elena Bestoso, Dania Tocci, Anna Sicuranza and Monica Bocchia

Volume 17, Issue 2, 2022

Published on: 15 July, 2022

Page: [92 - 96] Pages: 5

DOI: 10.2174/1574887117666220516145628

Price: $65

Open Access Journals Promotions 2
Abstract

Background: In the era of novel agents, many multiple myeloma patients can achieve a complete remission, but most of them relapse, and minimal residual disease detection can play a crucial role. Next-generation flow (NGF) can detect monoclonal plasma cells with a sensitivity of 10-6. Little is known about long-term remission patients (> 2 years) and in particular, if more sensitive techniques such as NGF can still detect minimal disease in those patients.

Objective: Aim of the study was to analyze patients with MM in response to NGF at > 2 years of sustained remission after several treatments.

Methods: MRD was studied by NGF in bone marrow aspirates according to Euroflow Consortium indications.

Results: 62 patients with sustained CR at >2 years were studied, MRD+ status was detected at a threshold cut-off of 10-6 in 32/62 (52%); 4/15 (27%) patients were MRD positive at >5 years of remission and they displayed a prevalence of normal vs abnormal monoclonal plasma cell immune-phenotype (MGUS-like).

Conclusion: NGF is a powerful technique to detect MRD. Myeloma patients in prolonged sustained complete remission can show in high percentage an MRD negative status or MGUS like.

Keywords: Multiple myeloma, minimal residual disease, next-generation flow, complete remission, monoclonal plasma cells, bone marrow.

« Previous
Graphical Abstract
[1]
Gozzetti, A.; Candi, V.; Papini, G.; Bocchia, M. Therapeutic advancements in multiple myeloma. Front. Oncol., 2014, 4, 241.
[http://dx.doi.org/10.3389/fonc.2014.00241] [PMID: 25237651]
[2]
Ocio, E.M.; Richardson, P.G.; Rajkumar, S.V. New drugs and novel mechanisms of action in multiple myeloma in 2013: A report from the International Myeloma Working Group (IMWG). Leukemia, 2014, 28(3), 525-542.
[http://dx.doi.org/10.1038/leu.2013.350] [PMID: 24253022]
[3]
Mohty, M.; Terpos, E.; Mateos, M.V. Multiple myeloma treatment in real-world clinical practice: Results of a prospective, multinational, noninterventional study. Clin. Lymphoma Myeloma Leuk., 2018, 18(10), e401-e419.
[http://dx.doi.org/10.1016/j.clml.2018.06.018] [PMID: 30030033]
[4]
Kumar, S.K.; Rajkumar, S.V.; Dispenzieri, A. Improved survival in multiple myeloma and the impact of novel therapies. Blood, 2008, 111(5), 2516-2520.
[http://dx.doi.org/10.1182/blood-2007-10-116129] [PMID: 17975015]
[5]
Castillo, J.J.; Jurczyszyn, A.; Brozova, L. IgM myeloma: A multicenter retrospective study of 134 patients. Am. J. Hematol., 2017, 92(8), 746-751.
[http://dx.doi.org/10.1002/ajh.24753] [PMID: 28383205]
[6]
Jurczyszyn, A.; Radocha, J.; Davila, J. Prognostic indicators in primary plasma cell leukaemia: A multicentre retrospective study of 117 patients. Br. J. Haematol., 2018, 180(6), 831-839.
[http://dx.doi.org/10.1111/bjh.15092] [PMID: 29315478]
[7]
Gozzetti, A.; Cerase, A. Novel agents in CNS myeloma treatment. Cent. Nerv. Syst. Agents Med. Chem., 2014, 14(1), 23-27.
[http://dx.doi.org/10.2174/1871524914999140818111514] [PMID: 25134940]
[8]
Cini, M.; Zamagni, E.; Valdré, L. Thalidomide-dexamethasone as up-front therapy for patients with newly diagnosed multiple myeloma: Thrombophilic alterations, thrombotic complications, and thromboprophylaxis with low-dose warfarin. Eur. J. Haematol., 2010, 84(6), 484-492.
[http://dx.doi.org/10.1111/j.1600-0609.2010.01434.x] [PMID: 20192986]
[9]
Gozzetti, A.; Bacchiarri, F.; Sammartano, V. Long-term safety of rapid daratumumab infusions in multiple myeloma patients. Front. Oncol., 2020, 10, 570187.
[http://dx.doi.org/10.3389/fonc.2020.570187] [PMID: 33415072]
[10]
Kumar, S.; Paiva, B.; Anderson, K.C. International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma. Lancet Oncol., 2016, 17(8), e328-e346.
[http://dx.doi.org/10.1016/S1470-2045(16)30206-6] [PMID: 27511158]
[11]
Gozzetti, A.; Raspadori, D.; Bacchiarri, F. Minimal residual disease in multiple myeloma: State of the art and applications in clinical practice. J. Pers. Med., 2020, 10(3), 120.
[http://dx.doi.org/10.3390/jpm10030120] [PMID: 32927719]
[12]
Flores-Montero, J.; Sanoja-Flores, L.; Paiva, B. Next Generation Flow for highly sensitive and standardized detection of minimal residual disease in multiple myeloma. Leukemia, 2017, 31(10), 2094-2103.
[http://dx.doi.org/10.1038/leu.2017.29] [PMID: 28104919]
[13]
Rawstron, A.C.; Orfao, A.; Beksac, M. Report of the European Myeloma Network on multiparametric flow cytometry in multiple myeloma and related disorders. Haematologica, 2008, 93(3), 431-438.
[http://dx.doi.org/10.3324/haematol.11080] [PMID: 18268286]
[14]
Brooimans, R.A.; Kraan, J.; van Putten, W.; Cornelissen, J.J.; Löwenberg, B.; Gratama, J.W. Flow cytometric differential of leukocyte populations in normal bone marrow: Influence of peripheral blood contamination. Cytometry B Clin. Cytom., 2009, 76(1), 18-26.
[http://dx.doi.org/10.1002/cyto.b.20439] [PMID: 18942105]
[15]
Gupta, R.; Bhaskar, A.; Kumar, L.; Sharma, A.; Jain, P. Flow cytometric immunophenotyping and minimal residual disease analysis in multiple myeloma. Am. J. Clin. Pathol., 2009, 132(5), 728-732.
[http://dx.doi.org/10.1309/AJCP1GYI7EHQYUYK] [PMID: 19846814]
[16]
Delgado, J.A.; Guillén-Grima, F.; Moreno, C. A simple flow-cytometry method to evaluate peripheral blood contamination of bone marrow aspirates. J. Immunol. Methods, 2017, 442, 54-58.
[http://dx.doi.org/10.1016/j.jim.2016.12.006] [PMID: 28041941]
[17]
Loken, M.R.; Chu, S.C.; Fritschle, W.; Kalnoski, M.; Wells, D.A. Normalization of bone marrow aspirates for hemodilution in flow cytometric analyses. Cytometry B Clin. Cytom., 2009, 76(1), 27-36.
[http://dx.doi.org/10.1002/cyto.b.20429] [PMID: 18548614]
[18]
Lionetti, M.; Neri, A. Utilizing next-generation sequencing in the management of multiple myeloma. Expert Rev. Mol. Diagn., 2017, 17(7), 653-663.
[http://dx.doi.org/10.1080/14737159.2017.1332996] [PMID: 28524737]
[19]
Bai, Y.; Orfao, A.; Chim, C.S. Molecular detection of minimal residual disease in multiple myeloma. Br. J. Haematol., 2018, 181(1), 11-26.
[http://dx.doi.org/10.1111/bjh.15075] [PMID: 29265356]
[20]
Yao, Q.; Bai, Y.; Orfao, A.; Chim, C.S. Standardized minimal residual disease detection by next-generation sequencing in multiple myeloma. Front. Oncol., 2019, 9, 449.
[http://dx.doi.org/10.3389/fonc.2019.00449] [PMID: 31245284]
[21]
Perrot, A.; Lauwers-Cances, V.; Corre, J. Minimal residual disease negativity using deep sequencing is a major prognostic factor in multiple myeloma. Blood, 2018, 132(23), 2456-2464.
[http://dx.doi.org/10.1182/blood-2018-06-858613] [PMID: 30249784]
[22]
Terpos, E.; Kostopoulos, I.V.; Kastritis, E. Impact of minimal residual disease detection by next-generation flow cytometry in multiple myeloma patients with sustained complete remission after frontline therapy. HemaSphere, 2019, 3(6), e300.
[http://dx.doi.org/10.1097/HS9.0000000000000300] [PMID: 31976475]
[23]
Munshi, N.C.; Avet-Loiseau, H.; Rawstron, A.C. Association of minimal residual disease with superior survival outcomes in patients with multiple myeloma: A meta-analysis. JAMA Oncol., 2017, 3(1), 28-35.
[http://dx.doi.org/10.1001/jamaoncol.2016.3160] [PMID: 27632282]
[24]
Paiva, B.; Vídriales, M.B.; Rosiñol, L. A multiparameter flow cytometry immunophenotypic algorithm for the identification of newly diagnosed symptomatic myeloma with an MGUS-like signature and long-term disease control. Leukemia, 2013, 27(10), 2056-2061.
[http://dx.doi.org/10.1038/leu.2013.166] [PMID: 23743858]
[25]
Pérez-Persona, E.; Vidriales, M.B.; Mateo, G. New criteria to identify risk of progression in monoclonal gammopathy of uncertain significance and smoldering multiple myeloma based on multiparameter flow cytometry analysis of bone marrow plasma cells. Blood, 2007, 110(7), 2586-2592.
[http://dx.doi.org/10.1182/blood-2007-05-088443] [PMID: 17576818]
[26]
Kastritis, E.; Terpos, E.; Moulopoulos, L. Extensive bone marrow infiltration and abnormal free light chain ratio identifies patients with asymptomatic myeloma at high risk for progression to symptomatic disease. Leukemia, 2013, 27(4), 947-953.
[http://dx.doi.org/10.1038/leu.2012.309] [PMID: 23183429]
[27]
Larsen, J.T.; Kumar, S.K.; Dispenzieri, A.; Kyle, R.A.; Katzmann, J.A.; Rajkumar, S.V. Serum free light chain ratio as a biomarker for high-risk smoldering multiple myeloma. Leukemia, 2013, 27(4), 941-946.
[http://dx.doi.org/10.1038/leu.2012.296] [PMID: 23183428]
[28]
Mateos, M.V.; Kumar, S.; Dimopoulos, M.A. International Myeloma Working Group risk stratification model for Smoldering Multiple Myeloma (SMM). Blood Cancer J., 2020, 10(10), 102.
[http://dx.doi.org/10.1038/s41408-020-00366-3] [PMID: 33067414]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy