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Myeloma

Long-term results of the GIMEMA VEL-03-096 trial in MM patients receiving VTD consolidation after ASCT: MRD kinetics' impact on survival

Abstract

Polymerase chain reaction (PCR)-based minimal residual disease (MRD) analysis is a useful prognostic tool in multiple myeloma (MM), although its long-term impact still needs to be addressed. This report presents the updated results of the GIMEMA-VEL-03-096 trial. Thirty-nine MM patients receiving bortezomib–thalidomide–dexamethasone after autologous transplantation were monitored for MRD by both nested and real-time quantitative-PCR until relapse. Our data confirm the strong impact of MRD on survival: overall survival was 72% at 8 years median follow-up for patients in major MRD response versus 48% for those experiencing MRD persistence (P=0.041). In addition, MRD kinetics resulted predictive for relapse: indeed median remission duration was not reached for patients in major MRD response, 38 months for those experiencing MRD reappearance and 9 months for patients with MRD persistence (P<0.001). Moreover: (1) 26 patients achieving major MRD response (67%) benefit of excellent disease control (median TNT: 42 months); (2) MRD reappearance heralds relapse, with a TNT comparable to that of MRD persistence (9 versus 10 months, P=0.706); (3) the median lag between MRD reappearance and need for salvage treatment is 9 months. These results suggest the usefulness of a long-term MRD monitoring in MM patients and the need for maintenance or pre-emptive treatments ensuring durable responses.

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Acknowledgements

We would like to thank the patients, nurses, physicians and data managers (Tiziana Marangon, Debora Caldarazzo and Antonella Fiorillo). This work was supported by Progetto di Rilevante Interesse Nazionale (PRIN 2009) from Ministero Italiano dell' Università e della Ricerca (MIUR), Roma, Italy (code: 7.07.02.60 AE01), Progetti di Ricerca Finalizzata 2008, head unit: IRCCS Centro di Riferimento Oncologico della Basilicata (CROB), Rionero in Vulture (Potenza), Italy (code: 7.07.08.60 P49), Progetto di Ricerca Sanitaria Finalizzata 2008, head unit: Divisione di Ematologia S. Cortellazzo, A. O. S. Maurizio, Bolzano/Bozen, Italy, (code: 7.07.08.60 P51), Progetto di Ricerca Sanitaria Finalizzata 2009, head unit: Divisione di Ematologia S. Cortellazzo, A. O. S. Maurizio, Bolzano/Bozen, Italy (code: RF-2009-1469205), Progetto di Ricerca Sanitaria Finalizzata 2010 (head unit: Divisione di Ematologia, A. O. S. Maurizio, Bolzano/Bozen, Italy, code: RF-2010-2307262), Progetti di Ateneo 2012 - Finanziatore Compagnia di San Paolo (code: TO_call03_2012_0055), Fondi di Ricerca Locale, Università degli Studi di Torino, Torino, Italy and Fondazione Neoplasie del Sangue (FO. NE. SA),Torino, Italy.

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This manuscript is an original paper and has not submitted or published in its current format anywhere else.

Author Contributions

ML, AP and MB designed the study. SF and ML wrote the report. AP supervised the clinical conduction of the study and data analysis. ML, SF and DD supervised the laboratory procedures. SF, FC, MU, SC, CT and SO supervised data collection, analyzed the data, and reviewed and assisted in writing the manuscript. DD and EG undertook the experimental procedures. RP and SF did the statistical analysis. FC, MG, FR, TG, CG, AML, VC, TC, CC, LDR, FP, APF, PP and PM recruited the patients.

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Correspondence to S Ferrero.

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Competing interests

ML—Celgene, Jannsen Cilag, Mundipharma, Roche and Amgen: research funding, speaker's bureau. FC—Celgene and Jannsen Cilag: consultancy membership on an entity's Board of Directors and advisory committees. TC—Celgene: honoraria, research funding, Jannsen Cilag: honoraria. TG—Celgene: research funding. PM—Celgene: honoraria, research funding. MB—Celgene: consultancy, membership on an entity’s Board of Directors or advisory committees, research funding; Jannsen Cilag: consultancy, membership on an entity’s Board of Directors or advisory committees, research funding. AP—Bristol–Myers Squibb, Celgene, Janssen Pharmaceuticals, Onyx and Amgen: consultancy, honoraria. The remaining authors declare no conflict of interest.

Additional information

Data from interim analyses were presented as abstracts at the 2009, 2011 and 2013 American Society of Hematology (ASH) meetings and at the 2014 European Hematology Association (EHA) meeting.

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Ferrero, S., Ladetto, M., Drandi, D. et al. Long-term results of the GIMEMA VEL-03-096 trial in MM patients receiving VTD consolidation after ASCT: MRD kinetics' impact on survival. Leukemia 29, 689–695 (2015). https://doi.org/10.1038/leu.2014.219

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