Upfront stem cell transplantation for newly diagnosed multiple myeloma with del(17p) and t(4;14): a study from the CMWP-EBMT.


Journal

Bone marrow transplantation
ISSN: 1476-5365
Titre abrégé: Bone Marrow Transplant
Pays: England
ID NLM: 8702459

Informations de publication

Date de publication:
01 2021
Historique:
received: 28 05 2020
accepted: 17 07 2020
revised: 13 07 2020
pubmed: 28 7 2020
medline: 22 6 2021
entrez: 26 7 2020
Statut: ppublish

Résumé

We analyzed newly diagnosed multiple myeloma patients with del(17p) and/or t(4;14) undergoing either upfront single autologous (auto), tandem autologous (auto-auto) or tandem autologous/reduced-intensity allogeneic (auto-allo) stem cell transplantation. 623 patients underwent either auto (n = 446), auto-auto (n = 105), or auto-allo (n = 72) between 2000 and 2015. 46% of patients had t(4;14), 45% had del(17p) while 9% were reported having both abnormalities. Five-year overall survival (OS) was 51% (95% confidence interval [CI], 45-58%) for single auto, 60% (95% CI, 49-72%) for auto-auto, and 67% (95% CI, 53-80%) for auto-allo (p = 0.187). Five-year progression-free survival (PFS) was 17% (95% CI, 12-22%), 33% (95% CI, 22-43%), and 34% (95% CI, 21-38%; p = 0.048). Five-year relapse rate was 82, 63, and 56%, while non-relapse mortality was 1, 4, and 10%. In multivariable analysis, in t(4;14) with single auto as reference, auto-auto (hazard ratio [HR], 0.44; p = 0.007) and auto-allo (HR, 0.45; p = 0.018) were associated with better PFS. In terms of t(4;14) and OS, auto-auto appeared to improve outcome compared with single auto (HR, 0.49; p = 0.096). In del(17p), outcome in PFS was similar between single auto and auto-auto, while auto-allo appeared to improve PFS (HR, 0.65; p = 0.097). No significant difference in OS was identified between the groups in patients with del(17p).

Identifiants

pubmed: 32710010
doi: 10.1038/s41409-020-01007-w
pii: 10.1038/s41409-020-01007-w
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

210-217

Références

Moreau P, San Miguel J, Sonneveld P, Mateos MV, Zamagni E, Avet-Loiseau H, et al. Multiple myeloma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2017;28(suppl_4):iv52–iv61.
doi: 10.1093/annonc/mdx096
Palumbo A, Anderson K. Multiple myeloma. N. Engl J Med. 2011;364:1046–60.
doi: 10.1056/NEJMra1011442
Bergsagel PL, Mateos MV, Gutierrez NC, Rajkumar SV, San Miguel JF. Improving overall survival and overcoming adverse prognosis in the treatment of cytogenetically high-risk multiple myeloma. Blood. 2013;121:884–92.
doi: 10.1182/blood-2012-05-432203
Sonneveld P, Avet-Loiseau H, Lonial S, Usmani S, Siegel D, Anderson KC, et al. Treatment of multiple myeloma with high-risk cytogenetics: a consensus of the International Myeloma Working Group. Blood. 2016;127:2955–62.
doi: 10.1182/blood-2016-01-631200
Fonseca R, Bergsagel PL, Drach J, Shaughnessy J, Gutierrez N, Stewart AK, et al. International Myeloma Working Group molecular classification of multiple myeloma: spotlight review. Leukemia. 2009;23:2210–21.
doi: 10.1038/leu.2009.174
Robinson D, Kaura S, Kiely D, Hussein MA, Nersesyan K, Durie BG. Impact of novel treatments on multiple myeloma survival. Blood. 2014;124:5676.
doi: 10.1182/blood.V124.21.5676.5676
Joseph NS, Kaufman JL, Dhodapkar MV, Hofmeister CC, Almaula DK, Heffner LT, et al. Long-term follow-up results of lenalidomide, bortezomib, and dexamethasone induction therapy and risk-adapted maintenance approach in newly diagnosed multiple myeloma. J Clin Oncol. 2020; https://doi.org/10.1200/JCO.19.02515 .
Attal M, Harousseau JL, Stoppa AM, Sotto JJ, Fuzibet JG, Rossi JF, et al. A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma: Intergroupe Français du Myélome. N. Engl J Med. 1996;335:91–7.
doi: 10.1056/NEJM199607113350204
Moreau P, Attal M, Hulin C, Arnulf B, Belhadj K, Benboubker L, et al. Bortezomib, thalidomide, and dexamethasone with or without daratumumab before and after autologous stem-cell transplantation for newly diagnosed multiple myeloma (CASSIOPEIA): a randomised, open-label, phase 3 study. Lancet. 2019;394:29–38.
doi: 10.1016/S0140-6736(19)31240-1
Barlogie B, Jagannath S, Vesole DH, Naucke S, Cheson B, Mattox S, et al. Superiority of tandem autologous transplantation over standard therapy for previously untreated multiple myeloma. Blood. 1997;89:789–93.
doi: 10.1182/blood.V89.3.789
Cavo M, Pantani L, Petrucci MT, Patriarca F, Zamagni E, Donnarumma D, et al. Bortezomib-thalidomide-dexamethasone is superior to thalidomide-dexamethasone as consolidation therapy after autologous hematopoietic stem cell transplantation in patients with newly diagnosed multiple myeloma. Blood. 2012;120:9–19.
doi: 10.1182/blood-2012-02-408898
Attal M, Harousseau JL, Facon T, Guilhot F, Doyen C, Fuzibet JG, et al. Single versus double autologous stem-cell transplantation for multiple myeloma. N. Engl J Med. 2003;349:2495–502.
doi: 10.1056/NEJMoa032290
Cavo M, Gay FM, Patriarca F, Zamagni E, Montefusco V, Dozza L, et al. Double autologous stem cell transplantation significantly prolongs progression-free survival and overall survival in comparison with single autotransplantation in newly diagnosed multiple myeloma: an analysis of phase 3 EMN02/HO95 study. Blood. 2017;130(suppl 1):401.
Stadtmauer EA, Pasquini MC, Blackwell B, Hari P, Bashey A, Devine S, et al. Autologous transplantation, consolidation, and maintenance therapy in multiple myeloma: results of the BMT CTN 0702 trial. J Clin Oncol. 2019;37:589–97.
doi: 10.1200/JCO.18.00685
Boyd KD, Ross FM, Chiecchio L, Dagrada GP, Konn ZJ, Tapper WJ, et al. A novel prognostic model in myeloma based on co-segregating adverse FISH lesions and the ISS: analysis of patients treated in the MRC Myeloma IX trial. Leukemia. 2012;26:349–55.
doi: 10.1038/leu.2011.204
Hebraud B, Magrangeas F, Cleynen A, Lauwers-Cances V, Chretien ML, Hulin C, et al. Role of additional chromosomal changes in the prognostic value of t(4;14) and del(17p) in multiple myeloma: the IFM experience. Blood. 2015;125:2095–100.
doi: 10.1182/blood-2014-07-587964
Perrot A, Lauwers-Cances V, Tournay E, Hulin C, Chretien ML, Royer B, et al. Development and validation of a cytogenetic prognostic index predicting survival in multiple myeloma. J Clin Oncol. 2019;37:1657–65.
doi: 10.1200/JCO.18.00776
Attal M, Lauwers-Cances V, Hulin C, Leleu X, Caillot D, Escoffre M, et al. Lenalidomide, bortezomib, and dexamethasone with transplantation for myeloma. N. Engl J Med. 2017;376:1311–20.
doi: 10.1056/NEJMoa1611750
Saini N, Ma J, Milton DR, Patel R, Varma A, Bashir Q, et al. Impact of autologous transplantation in patients with multiple myeloma with t(11;14): a propensity-score matched analysis. Clin Cancer Res. 2019;25:6781–7.
doi: 10.1158/1078-0432.CCR-19-0706
Ziogas DC, Dimopoulos MA, Kastritis E. Prognostic factors for multiple myeloma in the era of novel therapies. Expert Rev Hematol. 2018;11:863–79.
doi: 10.1080/17474086.2018.1537776
Kumar SK, Rajkumar SV. The multiple myelomas - current concepts in cytogenetic classification and therapy. Nat Rev Clin Oncol. 2018;15:409–21.
doi: 10.1038/s41571-018-0018-y
Dhakal B, Szabo A, Chhabra S, Hamadani M, D’Souza A, Usmani SZ, et al. Autologous transplantation for newly diagnosed multiple myeloma in the era of novel agent induction: a systematic review and meta-analysis. JAMA Oncol. 2018;4:343–50.
doi: 10.1001/jamaoncol.2017.4600
Cavo M, Goldschmidt H, Rosinol L, Pantani L, Zweegman S, Salwender HJ, et al. Double vs single autologous stem cell transplantation for newly diagnosed multiple myeloma: long-term follow-up (10-years) analysis of randomized phase 3 studies. Blood. 2018;132(suppl 1):124.
doi: 10.1182/blood-2018-99-112899
Gagelmann N, Eikema DJ, Koster L, Caillot D, Pioltelli P, Lleonart JB, et al. Tandem Autologous stem cell transplantation improves outcomes in newly diagnosed multiple myeloma with extramedullary disease and high-risk cytogenetics: a study from the chronic malignancies working party of the European Society for Blood and Marrow Transplantation. Biol Blood Marrow Transpl. 2019;25:2134–42.
doi: 10.1016/j.bbmt.2019.07.004
Cavo M, Salwender H, Rosinol L, Moreau P, Petrucci MT, Blau IW, et al. Double vs single autologous stem cell transplantation after bortezomib-based induction regimens for multiple myeloma: an integrated analysis of patient-level data from phase European III studies. Blood. 2013;122:767.
doi: 10.1182/blood.V122.21.767.767
Voorhees PM, Kaufman JL, Laubach JP, Sborov DW, Reeves B, Rodriguez C, et al. Daratumumab, lenalidomide, bortezomib, & dexamethasone for transplant-eligible newly diagnosed multiple myeloma: GRIFFIN. Blood. 2020; https://doi.org/10.1182/blood.2020005288.
Gay F, Engelhardt M, Terpos E, Wäsch R, Giaccone L, Auner HW, et al. From transplant to novel cellular therapies in multiple myeloma: European Myeloma Network guidelines and future perspectives. Haematologica. 2018;103:197–211.
doi: 10.3324/haematol.2017.174573
Bruno B, Rotta M, Patriarca F, Mordini N, Allione B, Carnevale-Schianca F, et al. A comparison of allografting with autografting for newly diagnosed myeloma. N. Engl J Med. 2007;356:1110–20.
doi: 10.1056/NEJMoa065464
Kröger N, Badbaran A, Zabelina T, Ayuk F, Wolschke C, Alchalby H, et al. Impact of high-risk cytogenetics and achievement of molecular remission on long-term freedom from disease after autologous-allogeneic tandem transplantation in patients with multiple myeloma. Biol Blood Marrow Transpl. 2013;19:398–404.
doi: 10.1016/j.bbmt.2012.10.008
Knop S, Engelhardt M, Liebisch P, Meisner C, Holler E, Metzner B, et al. Allogeneic transplantation in multiple myeloma: long-term follow-up and cytogenetic subgroup analysis. Leukemia. 2019;33:2710–9.
doi: 10.1038/s41375-019-0537-2
Schönland SO, Iacobelli S, Koster L, Blaise D, Potter M, Cornelissen JJ, et al. Comparison of different upfront transplant strategies in multiple myeloma - a large registry study from Chronic Malignancies Working Party of EBMT. Blood. 2019;134(Supplement_1):324.
doi: 10.1182/blood-2019-128795
Costa L, Iacobelli S, Pasquini M, Modi R, Giaccone L, Blade J, et al. Long-term survival of 1338 MM patients treated with tandem autologous vs. autologous-allogeneic transplantation. Bone Marrow Transplant. 2020; https://doi.org/10.1038/s41409-020-0887-4 .
McCarthy PL, Holstein SA, Petrucci MT, Richardson PG, Hulin C, Tosi P, et al. Lenalidomide maintenance after autologous stem-cell transplantation in newly diagnosed multiple myeloma: a meta-analysis. J Clin Oncol. 2017;35:3279–89.
doi: 10.1200/JCO.2017.72.6679
Goldschmidt H, Lokhorst HM, Mai EK, van der Holt B, Blau IW, Zweegman S, et al. Bortezomib before and after high-dose therapy in myeloma: long-term results from the phase III HOVON-65/GMMG-HD4 trial. Leukemia. 2018;32:383–90.
doi: 10.1038/leu.2017.211
Gay F, Jackson G, Rosiñol L, Holstein SA, Moreau P, Spada S, et al. Maintenance treatment and survival in patients with myeloma: a systematic review and network meta-analysis. JAMA Oncol. 2018;4:1389–97.
doi: 10.1001/jamaoncol.2018.2961
Dimopoulos MA, Gay F, Schjesvold F, Beksac M, Hajek R, Weisel KC, et al. Oral ixazomib maintenance following autologous stem cell transplantation (TOURMALINE-MM3): a double-blind, randomised, placebo-controlled phase 3 trial. Lancet. 2019;393:253–64.
doi: 10.1016/S0140-6736(18)33003-4
Gran C, Wang J, Nahi H, Koster L, Gahrton G, Einsele H, et al. Treosulfan conditioning for allogeneic transplantation in multiple myeloma - improved overall survival in first line haematopoietic stem cell transplantation - a large retrospective study by the Chronic Malignancies Working Party of the EBMT. Br J Haematol. 2020; https://doi.org/10.1111/bjh.16642 .
Walker BA, Mavrommatis K, Wardell CP, Ashby TC, Bauer M, Davies F, et al. A high-risk, double-hit, group of newly diagnosed myeloma identified by genomic analysis. Leukemia. 2019;33:159–70.
doi: 10.1038/s41375-018-0196-8

Auteurs

Nico Gagelmann (N)

University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Diderik-Jan Eikema (DJ)

EBMT Statistical Unit and Data Office Leiden, Leiden, The Netherlands.

Liesbeth C de Wreede (LC)

Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands.

Alessandro Rambaldi (A)

Department of Oncology-Hematology, University of Milan and Azienda Socio Sanitaria Territoriale, Papa Giovanni XXIII, Bergamo, Italy.

Simona Iacobelli (S)

EBMT Statistical Unit and Data Office Leiden, Leiden, The Netherlands.

Linda Koster (L)

EBMT Statistical Unit and Data Office Leiden, Leiden, The Netherlands.

Denis Caillot (D)

Hôpital d'Enfants Dijon, Dijon, France.

Didier Blaise (D)

Institut Paoli-Calmettes, Marseille, France.

Péter Remémyi (P)

Dél-pesti Centrumkórház-Országos Hematológiai és Infektológiai Intézet, Budapest, Hungary.

Claude-Eric Bulabois (CE)

CHU Grenoble Alpes - Université Grenoble Alpes, Grenoble, France.

Jakob Passweg (J)

University Hospital Basel, Basel, Switzerland.

Xavier Leleu (X)

Hopital La Miletrie, Poitiers, France.

Samo Zver (S)

University Med. Center Ljubljana, Ljubljana, Slovenia.

Guido Kobbe (G)

Department of Hematology, University Hospital, Heinrich Heine University, Düsseldorf, Germany.

Per Ljungman (P)

Karolinska University Hospital, Stockholm, Sweden.

Patrice Chevallier (P)

CHU Nantes, Nantes, France.

Mark Ringhoffer (M)

Klinikum Karlsruhe gGmbH, Karlsruhe, Germany.

Murray Martin (M)

Leicester Royal Infirmary, Leicester, UK.

Urpu Salmenniemi (U)

Turku University Hospital, Turku, Finland.

Xavier Poiré (X)

Cliniques Universitaires St. Luc, Brussels, Belgium.

Stig Lenhoff (S)

Skanes University Hospital, Lund, Sweden.

Pietro Pioltelli (P)

Ospedale San Gerardo, Monza, Italy.

Nicola Mordini (N)

Az. Ospedaliera S. Croce e Carle, Cuneo, Italy.

Michel Delforge (M)

University Hospital Gasthuisberg, Leuven, Belgium.

Laurent Garderet (L)

Hôpital Saint Antoine, Paris, France.

Stefan Schönland (S)

University of Heidelberg, Heidelberg, Germany.

Ibrahim Yakoub-Agha (I)

CHU de Lille, LIRIC, INSERM U995, Université de Lille, 59000, Lille, France.

Nicolaus Kröger (N)

University Medical Center Hamburg-Eppendorf, Hamburg, Germany. nkroeger@uke.uni-hamburg.de.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female
Humans United States Aged Cross-Sectional Studies Medicare Part C
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH