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Minimal residual disease assessed by multiparameter flow cytometry in multiple myeloma: impact on outcome in the medical research council myeloma IX study

Minimal residual disease assessed by multiparameter flow cytometry in multiple myeloma: impact on outcome in the medical research council myeloma IX study
Minimal residual disease assessed by multiparameter flow cytometry in multiple myeloma: impact on outcome in the medical research council myeloma IX study
PURPOSE: To investigate the prognostic value of minimal residual disease (MRD) assessment in patients with multiple myeloma treated in the MRC (Medical Research Council) Myeloma IX trial.

PATIENTS AND METHODS: Multiparameter flow cytometry (MFC) was used to assess MRD after induction therapy (n = 378) and at day 100 after autologous stem-cell transplantation (ASCT; n = 397) in intensive-pathway patients and at the end of induction therapy in non-intensive-pathway patients (n = 245).

RESULTS: In intensive-pathway patients, absence of MRD at day 100 after ASCT was highly predictive of a favorable outcome (PFS, P < .001; OS, P = .0183). This outcome advantage was demonstrable in patients with favorable and adverse cytogenetics (PFS, P = .014 and P < .001, respectively) and in patients achieving immunofixation-negative complete response (CR; PFS, P = .0068). The effect of maintenance thalidomide was assessed, with the shortest PFS demonstrable in those MRD-positive patients who did not receive maintenance and longest in those who were MRD negative and did receive thalidomide (P < .001). Further analysis demonstrated that 28% of MRD-positive patients who received maintenance thalidomide became MRD negative. MRD assessment after induction therapy in the non-intensive-pathway patients did not seem to be predictive of outcome (PFS, P = .1).

CONCLUSION: MRD assessment by MFC was predictive of overall outcome in patients with myeloma undergoing ASCT. This predictive value was seen in patients achieving conventional CR as well as patients with favorable and adverse cytogenetics. The effects of maintenance strategies can also be evaluated, and our data suggest that maintenance thalidomide can eradicate MRD in some patients.

1527-7755
2540-2547
Rawstron, Andy C.
750da2c1-cd55-42c7-83d8-868f660fb38e
Child, J. Anthony
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de Tute, Ruth
f504b3af-3a4c-449c-8e96-8faaadacd96c
Davies, Faith E.
9ea9e143-ac51-431b-8cb5-57b8dc0a38af
Gregory, Walter M.
4a7a4c5a-0a88-4ba2-8f08-0c035dd0b6db
Bell, Sue E.
4a926468-0ec4-4191-9842-5e9117d07883
Szubert, Alexander J.
f83d6436-08ec-46ea-878a-14fa54b27dc0
Navarro-Coy, Nuria
ebb3a585-8981-4c34-bbcb-4d6b29369b16
Drayson, Mark T.
282a00f4-8edf-4075-a83c-272ffcce53e8
Feyler, Sylvia
2fe572ce-ca56-47bd-a47d-679cfc21ef45
Ross, Fiona M.
ec0958f8-b992-4e4a-b7e3-c474600390ba
Cook, Gordon
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Jackson, Graham H.
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Morgan, Gareth J.
d285dcf8-ac2c-4fe0-acf9-4787eb025939
Owen, Roger G.
5846329e-f7a0-44d9-ac7a-717fb76ff9b5
Rawstron, Andy C.
750da2c1-cd55-42c7-83d8-868f660fb38e
Child, J. Anthony
1a7a739b-5295-4818-a455-3c67d9020abc
de Tute, Ruth
f504b3af-3a4c-449c-8e96-8faaadacd96c
Davies, Faith E.
9ea9e143-ac51-431b-8cb5-57b8dc0a38af
Gregory, Walter M.
4a7a4c5a-0a88-4ba2-8f08-0c035dd0b6db
Bell, Sue E.
4a926468-0ec4-4191-9842-5e9117d07883
Szubert, Alexander J.
f83d6436-08ec-46ea-878a-14fa54b27dc0
Navarro-Coy, Nuria
ebb3a585-8981-4c34-bbcb-4d6b29369b16
Drayson, Mark T.
282a00f4-8edf-4075-a83c-272ffcce53e8
Feyler, Sylvia
2fe572ce-ca56-47bd-a47d-679cfc21ef45
Ross, Fiona M.
ec0958f8-b992-4e4a-b7e3-c474600390ba
Cook, Gordon
4fe17be9-5e4e-4a58-a09a-b76f07f410f4
Jackson, Graham H.
82e8cc2d-7530-4b02-8f92-176f47451839
Morgan, Gareth J.
d285dcf8-ac2c-4fe0-acf9-4787eb025939
Owen, Roger G.
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Rawstron, Andy C., Child, J. Anthony, de Tute, Ruth, Davies, Faith E., Gregory, Walter M., Bell, Sue E., Szubert, Alexander J., Navarro-Coy, Nuria, Drayson, Mark T., Feyler, Sylvia, Ross, Fiona M., Cook, Gordon, Jackson, Graham H., Morgan, Gareth J. and Owen, Roger G. (2013) Minimal residual disease assessed by multiparameter flow cytometry in multiple myeloma: impact on outcome in the medical research council myeloma IX study. Journal of Clinical Oncology, 31 (20), 2540-2547. (doi:10.1200/JCO.2012.46.2119). (PMID:23733781)

Record type: Article

Abstract

PURPOSE: To investigate the prognostic value of minimal residual disease (MRD) assessment in patients with multiple myeloma treated in the MRC (Medical Research Council) Myeloma IX trial.

PATIENTS AND METHODS: Multiparameter flow cytometry (MFC) was used to assess MRD after induction therapy (n = 378) and at day 100 after autologous stem-cell transplantation (ASCT; n = 397) in intensive-pathway patients and at the end of induction therapy in non-intensive-pathway patients (n = 245).

RESULTS: In intensive-pathway patients, absence of MRD at day 100 after ASCT was highly predictive of a favorable outcome (PFS, P < .001; OS, P = .0183). This outcome advantage was demonstrable in patients with favorable and adverse cytogenetics (PFS, P = .014 and P < .001, respectively) and in patients achieving immunofixation-negative complete response (CR; PFS, P = .0068). The effect of maintenance thalidomide was assessed, with the shortest PFS demonstrable in those MRD-positive patients who did not receive maintenance and longest in those who were MRD negative and did receive thalidomide (P < .001). Further analysis demonstrated that 28% of MRD-positive patients who received maintenance thalidomide became MRD negative. MRD assessment after induction therapy in the non-intensive-pathway patients did not seem to be predictive of outcome (PFS, P = .1).

CONCLUSION: MRD assessment by MFC was predictive of overall outcome in patients with myeloma undergoing ASCT. This predictive value was seen in patients achieving conventional CR as well as patients with favorable and adverse cytogenetics. The effects of maintenance strategies can also be evaluated, and our data suggest that maintenance thalidomide can eradicate MRD in some patients.

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e-pub ahead of print date: 3 June 2013
Published date: 10 July 2013
Organisations: Human Development & Health

Identifiers

Local EPrints ID: 353643
URI: http://eprints.soton.ac.uk/id/eprint/353643
ISSN: 1527-7755
PURE UUID: e5360bf1-4ef7-4bd0-ac38-7f72405e8fd8

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Date deposited: 12 Jun 2013 14:31
Last modified: 27 Apr 2022 04:10

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Contributors

Author: Andy C. Rawstron
Author: J. Anthony Child
Author: Ruth de Tute
Author: Faith E. Davies
Author: Walter M. Gregory
Author: Sue E. Bell
Author: Alexander J. Szubert
Author: Nuria Navarro-Coy
Author: Mark T. Drayson
Author: Sylvia Feyler
Author: Fiona M. Ross
Author: Gordon Cook
Author: Graham H. Jackson
Author: Gareth J. Morgan
Author: Roger G. Owen

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