User menu

Accès à distance ? S'identifier sur le proxy UCLouvain

A systematic literature review and network meta-analysis of treatments for patients with untreated multiple myeloma not eligible for stem cell transplantation.

Primary tabs

Weisel, Katja Doyen, Chantal [UCL] Dimopoulos, Meletios Yee, Adrian Lahuerta, Juan José Facon, Thierry

In newly diagnosed multiple myeloma (MM), patients ineligible for front-line autologous stem cell transplantation (ASCT), melphalan and prednisone (MP) with thalidomide (MPT) or bortezomib (VMP) are standard first-line therapeutic options. Despite new treatment regimens incorporating bortezomib or lenalidomide, MM remains incurable. The FIRST study demonstrated significant improvement in progression-free survival (PFS) and overall survival (OS) for the combination of lenalidomide and low-dose dexamethasone (Rd) until progression vs. MPT in transplant-ineligible ndMM patients. However, to date no head-to-head randomized controlled trials (RCTs) have compared Rd or MPT versus VMP. We conducted a network meta-analysis using RCTs identified through a systematic literature review to evaluate the relative efficacy of Rd versus other regimens on survival endpoints in previously untreated MM patients ineligible for ASCT. In this analysis, Rd was associated with a significant PFS and survival advantage versus other first-line treatments (VMP, MPT, MP), challenging the role of alkylators in this setting.

Document type Article de périodique (Journal article) – Article de recherche
Access type Accès restreint
Publication date 2017
Language Anglais
Journal information "Leukemia and Lymphoma" - Vol. 58, no. 1, p. 153-161 (2017)
Peer reviewed yes
Publisher Informa Healthcare ((United Kingdom) London)
issn 1042-8194
e-issn 1029-2403
Publication status Publié
Affiliations UCL - SSS/IREC/MONT - Pôle Mont Godinne
UCL - (MGD) Service d'hématologie
Keywords Lenalidomide ; Multiple myeloma ; Network meta-analysis ; Systematic review
Links
  1. McCarthy Philip L., Palumbo Antonio, Maintenance Therapy for Multiple Myeloma, 10.1016/j.hoc.2014.06.006
  2. Faiman B, J Adv Pract Oncol, 5, 193 (2014)
  3. Engelhardt M., Terpos E., Kleber M., Gay F., Wasch R., Morgan G., Cavo M., van de Donk N., Beilhack A., Bruno B., Johnsen H. E., Hajek R., Driessen C., Ludwig H., Beksac M., Boccadoro M., Straka C., Brighen S., Gramatzki M., Larocca A., Lokhorst H., Magarotto V., Morabito F., Dimopoulos M. A., Einsele H., Sonneveld P., Palumbo A., , European Myeloma Network recommendations on the evaluation and treatment of newly diagnosed patients with multiple myeloma, 10.3324/haematol.2013.099358
  4. Moreau Philippe, Rajkumar S. Vincent, “Should all eligible patients with multiple myeloma receive autologous stem-cell transplant as part of initial treatment?”, 10.1016/j.leukres.2012.02.023
  5. Benboubker Lotfi, Dimopoulos Meletios A., Dispenzieri Angela, Catalano John, Belch Andrew R., Cavo Michele, Pinto Antonello, Weisel Katja, Ludwig Heinz, Bahlis Nizar, Banos Anne, Tiab Mourad, Delforge Michel, Cavenagh Jamie, Geraldes Catarina, Lee Je-Jung, Chen Christine, Oriol Albert, de la Rubia Javier, Qiu Lugui, White Darrell J., Binder Daniel, Anderson Kenneth, Fermand Jean-Paul, Moreau Philippe, Attal Michel, Knight Robert, Chen Guang, Van Oostendorp Jason, Jacques Christian, Ervin-Haynes Annette, Avet-Loiseau Hervé, Hulin Cyrille, Facon Thierry, Lenalidomide and Dexamethasone in Transplant-Ineligible Patients with Myeloma, 10.1056/nejmoa1402551
  6. Ades A. E., A chain of evidence with mixed comparisons: models for multi-parameter synthesis and consistency of evidence, 10.1002/sim.1566
  7. Caldwell D. M, Simultaneous comparison of multiple treatments: combining direct and indirect evidence, 10.1136/bmj.331.7521.897
  8. Lu G., Ades A. E., Combination of direct and indirect evidence in mixed treatment comparisons, 10.1002/sim.1875
  9. Liberati A., Altman D. G, Tetzlaff J., Mulrow C., Gotzsche P. C, Ioannidis J. P A, Clarke M., Devereaux P J, Kleijnen J., Moher D., The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration, 10.1136/bmj.b2700
  10. Tierney Jayne F, Stewart Lesley A, Ghersi Davina, Burdett Sarah, Sydes Matthew R, Practical methods for incorporating summary time-to-event data into meta-analysis, 10.1186/1745-6215-8-16
  11. Higgins J. P. T., Altman D. G., Gotzsche P. C., Juni P., Moher D., Oxman A. D., Savovic J., Schulz K. F., Weeks L., Sterne J. A. C., , , The Cochrane Collaboration's tool for assessing risk of bias in randomised trials, 10.1136/bmj.d5928
  12. Summary of Product Characteristics, REVLIMID, February 2015.
  13. Summary of Product Characteristics, VELCADE, April 2014.
  14. Summary of Product Characteristics, THALIDOMIDE, April 2013.
  15. Dias Sofia, Sutton Alex J., Ades A. E., Welton Nicky J., Evidence Synthesis for Decision Making 2 : A Generalized Linear Modeling Framework for Pairwise and Network Meta-analysis of Randomized Controlled Trials, 10.1177/0272989x12458724
  16. Facon Thierry, Mary Jean Yves, Hulin Cyrille, Benboubker Lotfi, Attal Michel, Pegourie Brigitte, Renaud Marc, Harousseau Jean Luc, Guillerm Gaëlle, Chaleteix Carine, Dib Mamoun, Voillat Laurent, Maisonneuve Hervé, Troncy Jacques, Dorvaux Véronique, Monconduit Mathieu, Martin Claude, Casassus Philippe, Jaubert Jérôme, Jardel Henry, Doyen Chantal, Kolb Brigitte, Anglaret Bruno, Grosbois Bernard, Yakoub-Agha Ibrahim, Mathiot Claire, Avet-Loiseau Hervé, Melphalan and prednisone plus thalidomide versus melphalan and prednisone alone or reduced-intensity autologous stem cell transplantation in elderly patients with multiple myeloma (IFM 99–06): a randomised trial, 10.1016/s0140-6736(07)61537-2
  17. Hulin Cyrille, Facon Thierry, Rodon Philippe, Pegourie Brigitte, Benboubker Lotfi, Doyen Chantal, Dib Mamoun, Guillerm Gaelle, Salles Bruno, Eschard Jean-Paul, Lenain Pascal, Casassus Philippe, Azaïs Isabelle, Decaux Olivier, Garderet Laurent, Mathiot Claire, Fontan Jean, Lafon Ingrid, Virion Jean Marc, Moreau Philippe, Efficacy of Melphalan and Prednisone Plus Thalidomide in Patients Older Than 75 Years With Newly Diagnosed Multiple Myeloma: IFM 01/01 Trial, 10.1200/jco.2008.21.0948
  18. Sacchi Stefano, Marcheselli Raffaella, Lazzaro Antonio, Morabito Fortunato, Fragasso Alberto, Renzo Nicola Di, Balleari Enrico, Neri Santo, Quarta Giovanni, Ferrara Raimondo, Vigliotti Maria Luigia, Polimeno Giuseppe, Musto Pellegrino, Consoli Ugo, Zoboli Alessandra, Buda Gabriele, Pastorini Alessandro, Masini Luciano, A randomized trial with melphalan and prednisone versus melphalan and prednisone plus thalidomide in newly diagnosed multiple myeloma patients not eligible for autologous stem cell transplant, 10.3109/10428194.2011.584006
  19. Brooks Stephen P., Gelman Andrew, General Methods for Monitoring Convergence of Iterative Simulations, 10.1080/10618600.1998.10474787
  20. Gelman A., Markov chain Monte Carlo in practice, 1311 (1996)
  21. Facon T, Dimopoulos MA, Hulin C, et al. Updated overall survival analysis of the FIRST study: continuous lenalidomide plus low-dose dexamethasone vs melphalan, prednisone, and thalidomide in patients with newly diagnosed multiple myeloma. Haematologica. 2015;100:3 (Abstract S105).
  22. Beksac Meral, Haznedar Rauf, Firatli-Tuglular Tulin, Ozdogu Hakan, Aydogdu Ismet, Konuk Nahide, Sucak Gulsan, Kaygusuz Işık, Karakus Sema, Kaya Emin, Ali Ridvan, Gulbas Zafer, Ozet Gulsum, Goker Hakan, Undar Levent, Addition of thalidomide to oral melphalan/prednisone in patients with multiple myeloma not eligible for transplantation: results of a randomized trial from the Turkish Myeloma Study Group : Addition of thalidomide to oral melphalan/prednisone in patients with multiple myeloma, 10.1111/j.1600-0609.2010.01524.x
  23. Facon T., Dexamethasone-based regimens versus melphalan-prednisone for elderly multiple myeloma patients ineligible for high-dose therapy, 10.1182/blood-2005-04-1588
  24. Mateos María-Victoria, Oriol Albert, Martínez-López Joaquín, Gutiérrez Norma, Teruel Ana-Isabel, de Paz Raquel, García-Laraña José, Bengoechea Enrique, Martín Alejandro, Mediavilla Joaquín Díaz, Palomera Luis, de Arriba Felipe, González Yolanda, Hernández Jose-Mariano, Sureda Ana, Bello José-Luis, Bargay Joan, Peñalver Francisco-Javier, Ribera José-María, Martín-Mateos María-Luisa, García-Sanz Ramón, Cibeira María-Teresa, Ramos María-Luisa Martín, Vidriales María-Belén, Paiva Bruno, Montalbán María-Angeles, Lahuerta Juan-José, Bladé Joan, Miguel Jesús-Fernando San, Bortezomib, melphalan, and prednisone versus bortezomib, thalidomide, and prednisone as induction therapy followed by maintenance treatment with bortezomib and thalidomide versus bortezomib and prednisone in elderly patients with untreated multiple myeloma: a randomised trial, 10.1016/s1470-2045(10)70187-x
  25. Morgan G. J., Davies F. E., Gregory W. M., Russell N. H., Bell S. E., Szubert A. J., Coy N. N., Cook G., Feyler S., Byrne J. L., Roddie H., Rudin C., Drayson M. T., Owen R. G., Ross F. M., Jackson G. H., Child J. A., , Cyclophosphamide, thalidomide, and dexamethasone (CTD) as initial therapy for patients with multiple myeloma unsuitable for autologous transplantation, 10.1182/blood-2011-02-338665
  26. Palumbo A., Bringhen S., Liberati A. M., Caravita T., Falcone A., Callea V., Montanaro M., Ria R., Capaldi A., Zambello R., Benevolo G., Derudas D., Dore F., Cavallo F., Gay F., Falco P., Ciccone G., Musto P., Cavo M., Boccadoro M., Oral melphalan, prednisone, and thalidomide in elderly patients with multiple myeloma: updated results of a randomized controlled trial, 10.1182/blood-2008-04-149427
  27. Palumbo Antonio, Bringhen Sara, Rossi Davide, Cavalli Maide, Larocca Alessandra, Ria Roberto, Offidani Massimo, Patriarca Francesca, Nozzoli Chiara, Guglielmelli Tommasina, Benevolo Giulia, Callea Vincenzo, Baldini Luca, Morabito Fortunato, Grasso Mariella, Leonardi Giovanna, Rizzo Manuela, Pia Falcone Antonietta, Gottardi Daniela, Montefusco Vittorio, Musto Pellegrino, Petrucci Maria Teresa, Ciccone Giovannino, Boccadoro Mario, Bortezomib-Melphalan-Prednisone-Thalidomide Followed by Maintenance With Bortezomib-Thalidomide Compared With Bortezomib-Melphalan-Prednisone for Initial Treatment of Multiple Myeloma: A Randomized Controlled Trial, 10.1200/jco.2010.29.8216
  28. Palumbo Antonio, Hajek Roman, Delforge Michel, Kropff Martin, Petrucci Maria Teresa, Catalano John, Gisslinger Heinz, Wiktor-Jędrzejczak Wiesław, Zodelava Mamia, Weisel Katja, Cascavilla Nicola, Iosava Genadi, Cavo Michele, Kloczko Janusz, Bladé Joan, Beksac Meral, Spicka Ivan, Plesner Torben, Radke Joergen, Langer Christian, Yehuda Dina Ben, Corso Alessandro, Herbein Lindsay, Yu Zhinuan, Mei Jay, Jacques Christian, Dimopoulos Meletios A., Continuous Lenalidomide Treatment for Newly Diagnosed Multiple Myeloma, 10.1056/nejmoa1112704
  29. Magarotto V., Bringhen S., Offidani M., Benevolo G., Patriarca F., Mina R., Falcone A. P., De Paoli L., Pietrantuono G., Gentili S., Musolino C., Giuliani N., Bernardini A., Conticello C., Pulini S., Ciccone G., Maisnar V., Ruggeri M., Zambello R., Guglielmelli T., Ledda A., Liberati A. M., Montefusco V., Hajek R., Boccadoro M., Palumbo A., Triplet vs doublet lenalidomide-containing regimens for the treatment of elderly patients with newly diagnosed multiple myeloma, 10.1182/blood-2015-08-662627
  30. San Miguel Jesús F., Schlag Rudolf, Khuageva Nuriet K., Dimopoulos Meletios A., Shpilberg Ofer, Kropff Martin, Spicka Ivan, Petrucci Maria Teresa, Palumbo Antonio, Samoilova Olga S., Dmoszynska Anna, Abdulkadyrov Kudrat M., Delforge Michel, Jiang Bin, Mateos Maria-Victoria, Anderson Kenneth C., Esseltine Dixie-Lee, Liu Kevin, Deraedt William, Cakana Andrew, van de Velde Helgi, Richardson Paul G., Persistent Overall Survival Benefit and No Increased Risk of Second Malignancies With Bortezomib-Melphalan-Prednisone Versus Melphalan-Prednisone in Patients With Previously Untreated Multiple Myeloma, 10.1200/jco.2012.41.6180
  31. San-Miguel J., Blade J., Shpilberg O., Grosicki S., Maloisel F., Min C.-K., Polo Zarzuela M., Robak T., Prasad S. V. S. S., Tee Goh Y., Laubach J., Spencer A., Mateos M.-V., Palumbo A., Puchalski T., Reddy M., Uhlar C., Qin X., van de Velde H., Xie H., Orlowski R. Z., Phase 2 randomized study of bortezomib-melphalan-prednisone with or without siltuximab (anti-IL-6) in multiple myeloma, 10.1182/blood-2013-12-546374
  32. Waage A., Gimsing P., Fayers P., Abildgaard N., Ahlberg L., Bjorkstrand B., Carlson K., Dahl I. M., Forsberg K., Gulbrandsen N., Haukas E., Hjertner O., Hjorth M., Karlsson T., Knudsen L. M., Nielsen J. L., Linder O., Mellqvist U.-H., Nesthus I., Rolke J., Strandberg M., Sorbo J. H., Wisloff F., Juliusson G., Turesson I., , Melphalan and prednisone plus thalidomide or placebo in elderly patients with multiple myeloma, 10.1182/blood-2009-08-237974
  33. Wijermans Pierre, Schaafsma Martijn, Termorshuizen Fabian, Ammerlaan Rianne, Wittebol Shulamiet, Sinnige Harm, Zweegman Sonja, van Marwijk Kooy Marinus, van der Griend René, Lokhorst Henk, Sonneveld Pieter, Phase III Study of the Value of Thalidomide Added to Melphalan Plus Prednisone in Elderly Patients With Newly Diagnosed Multiple Myeloma: The HOVON 49 Study, 10.1200/jco.2009.26.1610
  34. Stewart AK, Jacobus S, Fonseca R, et al. E1A06: A phase III trial comparing melphalan, prednisone, and thalidomide (MPT) versus melphalan, prednisone, and lenalidomide (MPR) in newly diagnosed multiple myeloma (MM). Haematologica. 2014;99:220 (Abstract S642).
  35. Palumbo Antonio, Bringhen Sara, Caravita Tommaso, Merla Emanuela, Capparella Vincenzo, Callea Vincenzo, Cangialosi Clotilde, Grasso Mariella, Rossini Fausto, Galli Monica, Catalano Lucio, Zamagni Elena, Petrucci Maria Teresa, De Stefano Valerio, Ceccarelli Manuela, Ambrosini Maria Teresa, Avonto Ilaria, Falco Patrizia, Ciccone Giovannino, Liberati Anna Marina, Musto Pellegrino, Boccadoro Mario, Oral melphalan and prednisone chemotherapy plus thalidomide compared with melphalan and prednisone alone in elderly patients with multiple myeloma: randomised controlled trial, 10.1016/s0140-6736(06)68338-4
  36. San Miguel Jesús F., Schlag Rudolf, Khuageva Nuriet K., Dimopoulos Meletios A., Shpilberg Ofer, Kropff Martin, Spicka Ivan, Petrucci Maria T., Palumbo Antonio, Samoilova Olga S., Dmoszynska Anna, Abdulkadyrov Kudrat M., Schots Rik, Jiang Bin, Mateos Maria-Victoria, Anderson Kenneth C., Esseltine Dixie L., Liu Kevin, Cakana Andrew, van de Velde Helgi, Richardson Paul G., Bortezomib plus Melphalan and Prednisone for Initial Treatment of Multiple Myeloma, 10.1056/nejmoa0801479
  37. Fayers P. M., Palumbo A., Hulin C., Waage A., Wijermans P., Beksac M., Bringhen S., Mary J.-Y., Gimsing P., Termorshuizen F., Haznedar R., Caravita T., Moreau P., Turesson I., Musto P., Benboubker L., Schaafsma M., Sonneveld P., Facon T., , Thalidomide for previously untreated elderly patients with multiple myeloma: meta-analysis of 1685 individual patient data from 6 randomized clinical trials, 10.1182/blood-2011-03-341669
  38. Palumbo A., Waage A., Hulin C., Beksac M., Zweegman S., Gay F., Gimsing P., Leleu X., Wijermans P., Sucak G., Pezzatti S., Juliusson G., Pegourie B., Schaafsma M., Galli M., Turesson I., Kolb B., van der Holt B., Baldi I., Rolke J., Ciccone G., Wetterwald M., Lokhorst H., Boccadoro M., Rodon P., Sonneveld P., Safety of thalidomide in newly diagnosed elderly myeloma patients: a meta-analysis of data from individual patients in six randomized trials, 10.3324/haematol.2012.067058
  39. Zou Yandun, Sheng Zhixin, Niu Shaona, Wang Huijuan, Yu Jinming, Xu Jingbo, Lenalidomide versus thalidomide based regimens as first-line therapy for patients with multiple myeloma, 10.3109/10428194.2013.774393
  40. Morabito Fortunato, Bringhen Sara, Larocca Alessandra, Wijermans Pierre, Victoria Mateos Maria, Gimsing Peter, Mazzone Carla, Gottardi Daniela, Omedè Paola, Zweegman Sonja, José Lahuerta Juan, Zambello Renato, Musto Pellegrino, Magarotto Valeria, Schaafsma Martijn, Oriol Albert, Juliusson Gunnar, Cerrato Chiara, Catalano Lucio, Gentile Massimo, Isabel Turel Ana, Marina Liberati Anna, Cavalli Maide, Rossi Davide, Passera Roberto, Rosso Stefano, Beksac Meral, Cavo Michele, Waage Anders, San Miguel Jesus, Boccadoro Mario, Sonneveld Pieter, Palumbo Antonio, Offidani Massimo, Bortezomib, melphalan, prednisone (VMP) versus melphalan, prednisone, thalidomide (MPT) in elderly newly diagnosed multiple myeloma patients: A retrospective case-matched study : VMPversusMPT in Elderly MM Patients, 10.1002/ajh.23641
  41. Kumar Ambuj, Hozo Iztok, Wheatley Keath, Djulbegovic Benjamin, Thalidomide versus bortezomib based regimens as first-line therapy for patients with multiple myeloma: A systematic review, 10.1002/ajh.21904
  42. NICE technology appraisal guidance 228. Bortezomib and thalidomide for the first-line treatment of multiple myeloma; [cited 2011 Jul]. Available from: http://www.nice.org.uk/guidance/ta228.
  43. Delforge M., Minuk L., Eisenmann J.-C., Arnulf B., Canepa L., Fragasso A., Leyvraz S., Langer C., Ezaydi Y., Vogl D. T., Giraldo-Castellano P., Yoon S.-S., Zarnitsky C., Escoffre-Barbe M., Lemieux B., Song K., Bahlis N. J., Guo S., Monzini M. S., Ervin-Haynes A., Houck V., Facon T., Health-related quality-of-life in patients with newly diagnosed multiple myeloma in the FIRST trial: lenalidomide plus low-dose dexamethasone versus melphalan, prednisone, thalidomide, 10.3324/haematol.2014.120121
Bibliographic reference Weisel, Katja ; Doyen, Chantal ; Dimopoulos, Meletios ; Yee, Adrian ; Lahuerta, Juan José ; et. al. A systematic literature review and network meta-analysis of treatments for patients with untreated multiple myeloma not eligible for stem cell transplantation.. In: Leukemia and Lymphoma, Vol. 58, no. 1, p. 153-161 (2017)
Permanent URL http://hdl.handle.net/2078.1/174816