Minimal residual disease monitoring by 8-color flow cytometry in mantle cell lymphoma: an EU-MCL and LYSA study
Morgane Cheminant,
Coralie Derrieux,
Aurore Touzart,
Stéphanie Schmit,
Adrien Grenier,
Amélie Trinquand,
Marie-Hélène Delfau-Larue,
Ludovic Lhermitte,
Catherine Thieblemont,
Vincent Ribrag,
Stéphane Cheze,
Laurence Sanhes,
Fabrice Jardin,
François Lefrère,
Richard Delarue,
Eva Hoster,
Martin Dreyling,
Vahid Asnafi,
Olivier Hermine,
Elizabeth Macintyre
Affiliations
Morgane Cheminant
Biological Hematology, Paris Descartes – Sorbonne Paris Cité University, Institut Necker-Enfants Malades, AP-HP, France;Clinical Hematology, Paris Descartes – Sorbonne Paris Cité University, IMAGINE Institut, Necker Hospital, AP-HP, France
Coralie Derrieux
Biological Hematology, Paris Descartes – Sorbonne Paris Cité University, Institut Necker-Enfants Malades, AP-HP, France
Aurore Touzart
Biological Hematology, Paris Descartes – Sorbonne Paris Cité University, Institut Necker-Enfants Malades, AP-HP, France
Stéphanie Schmit
Biological Hematology, Paris Descartes – Sorbonne Paris Cité University, Institut Necker-Enfants Malades, AP-HP, France
Adrien Grenier
Biological Hematology, Paris Descartes – Sorbonne Paris Cité University, Institut Necker-Enfants Malades, AP-HP, France
Amélie Trinquand
Biological Hematology, Paris Descartes – Sorbonne Paris Cité University, Institut Necker-Enfants Malades, AP-HP, France
Marie-Hélène Delfau-Larue
Biological Hematology and Immunology, AP-HP, Groupe Hospitalier Mondor, Créteil, France
Ludovic Lhermitte
Biological Hematology, Paris Descartes – Sorbonne Paris Cité University, Institut Necker-Enfants Malades, AP-HP, France
Catherine Thieblemont
Hemato-Oncology, Saint-Louis Hospital, APHP – Paris Diderot – Sorbonne Paris Cité University - INSERM U728 – Institut Universitaire d’Hematologie, France
Vincent Ribrag
Département de Médecine, Institut Gustave Roussy, Villejuif, France
Stéphane Cheze
Clinical Hematology, University Hospital of Caen, France
Laurence Sanhes
Clinical Hematology, Perpignan Hospital, France
Fabrice Jardin
Clinical Hematology, INSERM U918, IRIB, Centre Henri Becquerel, Rouen, France
François Lefrère
Clinical Hematology, Paris Descartes – Sorbonne Paris Cité University, IMAGINE Institut, Necker Hospital, AP-HP, France
Richard Delarue
Clinical Hematology, Paris Descartes – Sorbonne Paris Cité University, IMAGINE Institut, Necker Hospital, AP-HP, France
Eva Hoster
Institute of Medical Informatics, Biometry, and Epidemiology, University of Munich, Germany;Department of Internal Medicine III, University Hospital Munich, Germany
Martin Dreyling
Department of Internal Medicine III, University Hospital Munich, Germany
Vahid Asnafi
Biological Hematology, Paris Descartes – Sorbonne Paris Cité University, Institut Necker-Enfants Malades, AP-HP, France
Olivier Hermine
Clinical Hematology, Paris Descartes – Sorbonne Paris Cité University, IMAGINE Institut, Necker Hospital, AP-HP, France
Elizabeth Macintyre
Biological Hematology, Paris Descartes – Sorbonne Paris Cité University, Institut Necker-Enfants Malades, AP-HP, France
Quantification of minimal residual disease may guide therapeutic strategies in mantle cell lymphoma. While multiparameter flow cytometry is used for diagnosis, the gold standard method for minimal residual disease analysis is real-time quantitative polymerase chain reaction (RQ-PCR). In this European Mantle Cell Lymphoma network (EU-MCL) pilot study, we compared flow cytometry with RQ-PCR for minimal residual disease detection. Of 113 patients with at least one minimal residual disease sample, RQ-PCR was applicable in 97 (86%). A total of 284 minimal residual disease samples from 61 patients were analyzed in parallel by flow cytometry and RQ-PCR. A single, 8-color, 10-antibody flow cytometry tube allowed specific minimal residual disease assessment in all patients, with a robust sensitivity of 0.01%. Using this cut-off level, the true-positive-rate of flow cytometry with respect to RQ-PCR was 80%, whereas the true-negative-rate was 92%. As expected, RQ-PCR frequently detected positivity below this 0.01% threshold, which is insufficiently sensitive for prognostic evaluation and would ideally be replaced with robust quantification down to a 0.001% (10-5) threshold. In 10 relapsing patients, the transition from negative to positive by RQ-PCR (median 22.5 months before relapse) nearly always preceded transition by flow cytometry (4.5 months), but transition to RQ-PCR positivity above 0.01% (5 months) was simultaneous. Pre-emptive rituximab treatment of 2 patients at minimal residual disease relapse allowed re-establishment of molecular and phenotypic complete remission. Flow cytometry minimal residual disease is a complementary approach to RQ-PCR and a promising tool in individual mantle cell lymphoma therapeutic management.
