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Prospective molecular monitoring of minimal residual disease after non-myeloablative allografting in newly diagnosed multiple myeloma

Leukemia volume 30, pages 1211–1214 (2016)Cite this article

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Allografting is potentially curative for myeloma (MM).1 Molecular remissions (MR) were reported after myeloablative and reduced-intensity conditionings.2, 3 Before the ‘new drugs’ era, a tandem approach with an autograft after high-dose melphalan (200 mg/m2) followed by a non-myeloablative 200 cGy total body irradiation-based allograft was designed in Seattle.4 At a median follow-up of 12.1 years, we report long-term clinical outcomes of minimal residual disease (MRD) kinetics by qualitative PCR (nested-PCR) and real-time quantitative PCR (qPCR) on a cohort of newly diagnosed patients treated with the Seattle approach.

Between December 1999 and July 2009, 26 patients (Supplementary Table S1) with suitable diagnostic bone marrow (BM) specimens for immunoglobulin heavy-chain gene rearrangement (IGH) sequencing were prospectively monitored for MRD. Patients were induced with two to three courses of vincristine–adriamycin–dexamethasone-based regimens (20/26, 78%; ClinicalTrial.gov, NCT-00702247), with three courses of bortezomib-thalidomide-dexametasone (VTD; EudraCTNumber: 2007-003707-12; 2/26, 8%) or with four courses of lenalidomide–dexamethasone (4/26, 14%; ClinicalTrial.gov, NCT01264315) followed by the tandem transplant approach.4 No pre-emptive donor lymphocyte infusions or maintenance/consolidation treatment were allowed except for the four patients enrolled in protocol NCT01264315 who started lenalidomide–dexamethasone maintenance.

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Acknowledgements

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, A.O.S. Maurizio, Bolzano/Bozen, Italy; code: 7.07.08.60 P51), Progetto di Ricerca Sanitaria Finalizzata 2008 (code: RF-PIE-2008-1206999), Progetto di Ricerca Sanitaria Finalizzata 2009 (code: RF-2009-1491359), Progetto di Ricerca Sanitaria Finalizzata 2009, (head unit: Divisione di Ematologia, 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), Fondi di Ricerca Locale, Università degli Studi di Torino, Torino, Italy and by Fondazione Neoplasie del sangue (FO.NE. SA),Torino, Italy.

The authors would like to thank Maria Josè Fornaro, Antonella Fiorillo and Franca Trotto Gatta for excellent secretarial support.

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Authors and Affiliations

  1. Division of Hematology, A.O.U. Città della Salute e della Scienza di Torino, University of Torino, Torino, Italy

    M Ladetto, S Ferrero, D Drandi, M Festuccia, S Cena, R Benedetto, G Guarona, F Ferrando, L Brunello, P Ghione, V Boccasavia, P Omedè, L Giaccone, A Palumbo, M Boccadoro & B Bruno

  2. Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy

    M Ladetto, S Ferrero, D Drandi, M Festuccia, R Benedetto, G Guarona, L Brunello, P Ghione, L Giaccone, A Palumbo, M Boccadoro & B Bruno

  3. Azienda Ospedaliera SS Antonio e Biagio e Cesare Arrigo, Alessandria, Italy

    M Ladetto

  4. Division of Hematology, A.O.U, Udine, DISM, University of Udine, Udine, Italy

    F Patriarca & R Fanin

  5. Division of Hematology, Ospedale ‘S.Croce e Carle’, Cuneo, Italy

    N Mordini

  6. Division of Nuclear Medicine, Statistical Consultant, A.O.U. Città della Salute e della Scienza di Torino, Torino, Italy

    R Passera

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  1. M Ladetto
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Corresponding author

Correspondence to B Bruno.

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Competing interests

AP has received consultancy and honoraria from Amgen, Bristol-Myers Squibb, Celgene, Janssen, Millenium, Onyx; MB has received research support, consultancy and scientific advisory board for Celgene and Janssen-Cilag; ML has received research support from Janssen-Cilag, Amgen, Roche and Italfarmaco, and honoraria from Celgene, Roche, Bayer, Amgen and Mundipharma; SF has received speakers honoraria from Celgene and Mundipharma; BB has received honoraria from Gilead, Pfizer, Celgene, Hospira and research support form Celgene, Pierre Fabre, ADIENNE, Hospira Italia, MSD Italia. FP has received honararia from Celgene, Janssen, MSD Italia; Advisory Board for Mundipharma, Bristol MSD, Janssen. The remaining authors declare no conflict of interest.

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Ladetto, M., Ferrero, S., Drandi, D. et al. Prospective molecular monitoring of minimal residual disease after non-myeloablative allografting in newly diagnosed multiple myeloma. Leukemia 30, 1211–1214 (2016). https://doi.org/10.1038/leu.2015.269

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