Prognostic impact of early-versus-late responses to different induction regimens in patients with myeloma undergoing autologous hematopoietic cell transplantation: Results from the CALM study by the CMWP of the EBMT
Language English Country Great Britain, England Media print-electronic
Document type Journal Article
Grant support
UK NIHR Imperial college
PubMed
33580608
DOI
10.1111/ejh.13602
Knihovny.cz E-resources
- Keywords
- autologous transplantation, induction regimen, kinetics of response, multiple myeloma,
- MeSH
- Transplantation, Autologous MeSH
- Time Factors MeSH
- Remission Induction MeSH
- Humans MeSH
- Multiple Myeloma diagnosis mortality therapy MeSH
- Prognosis MeSH
- Antineoplastic Combined Chemotherapy Protocols adverse effects therapeutic use MeSH
- Hematopoietic Stem Cell Transplantation * adverse effects methods MeSH
- Duration of Therapy MeSH
- Treatment Outcome MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: In autologous stem cell transplant (ASCT)-eligible myeloma patients, prolonged induction does not necessarily improve the depth of response. METHOD: We analyzed 1222 ASCT patients who were classified based on (a) the interval between induction and stem cell collection, (b) the type of induction regimen: BID (Bortezomib, IMiDs, and Dexamethasone), Bortezomib-based, or CTD (Cyclophosphamide, Thalidomide, and Dexamethasone), and (c) the time to best response (Early ie, best response within 4 or 5 months, depending on the regimen vs Late; Good ie, VGPR or better vs Poor). RESULTS: The length of induction treatment required to achieve a Good response did not affect PFS (P = .65) or OS (P = .61) post-ASCT. The three types of regimen resulted in similar outcomes: median PFS 31, 27.7 and 30.8 months (P = .31), and median OS 81.7, 92.7, and 77.4 months, respectively (P = .83). On multivariate analysis, neither the type nor the duration of the induction regimen affected OS and PFS, except for Early Good Responders who had a better PFS compared to Early Poor Responders (HR = 1.21, P-value = .02). However, achieving a Good response at induction was associated with a better response (≥VGPR) post-transplant. CONCLUSION: The kinetics of response did not affect outcomes.
Ankara University Faculty of Medicine Ankara Turkey
C R O IRCCS Aviano Aviano Italy
Centre for Haematology Imperial College London UK
Chaim Sheba Medical Center Tel Hashomer Israel
Charles University Hospital Prague Czech Republic
Cliniques Universitaires St Luc Brussels Belgium
Dél pesti Centrumkórház Országos Hematológiai és Infektológiai Intézet Budapest Hungary
Department of Biology Tor Vergata University Rome
Department of Haematology Trinity College Dublin St James's Hospital Dublin 8 Ireland
EBMT Data Office Leiden Netherlands
Fundeni Clinical Institute Bucarest Romania
Hope Directorate St James's Hospital Dublin Ireland
Hospital Universitario Central de Asturias Oviedo Spain
ICO Hospital Duran 1 Reynals Barcelona Spain
Institut Paoli Calmettes Marseilles France
Medical Department 5 University Hospital Heidelberg Heidelberg Germany
Skanes University Hospital Lund Sweden
The Medical University of Warsaw Warsaw Poland
Umea University Hospital Umea Sweden
University Hospital Brno Brno Czech Republic
University Hospital of Lille Inserm CHU Lille INSERM Infinite Lille France
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Kyle RA, Rajkumar SV. Multiple myeloma. N Engl J Med. 2004;351:1860-1873.
Sonneveld P, Goldschmidt H, Rosinol L, et al. Bortezomib-based versus nonbortezomib-based induction treatment before autologous stem-cell transplantation in patients with previously untreated multiple myeloma: a meta-analysis of phase III randomized, controlled trials. J Clin Oncol. 2013;31:3279-3287.
Kumar SK, Lacy MQ, Dispenzieri A, et al. Early versus delayed autologous transplantation after immunomodulatory agents-based induction therapy in patients with newly diagnosed multiple myeloma. Cancer. 2012;118:1585-1592.
Pulte D, Redaniel MT, Brenner H, et al. Recent improvement in survival of patients with multiple myeloma: variation by ethnicity. Leuk Lymph. 2014;55:1083-1089.
Moreau P, Attal M, Pegourie B, et al. Achievement of VGPR to induction therapy is an important prognostic factor for longer PFS in the IFM 2005-01 trial. Blood. 2011;117:3041-3044.
Moreau P, San Miguel J, Sonneveld P, et al. Multiple myeloma: ESMO clinical practice guidelines for diagnosis, treatment and follow up dagger. Ann Oncol. 2017;28(suppl 4):iv52-iv61.
Rosinol L, Oriol A, Teruel AI, et al. Superiority of bortezomib, thalidomide, and dexamethasone (VTD) as induction pretransplantation therapy in multiple myeloma: a randomized phase 3 PETHEMA/GEM study. Blood. 2012;120:1589-1596.
Cavo M, Tacchetti P, Patriarca F, et al. Bortezomib with thalidomide plus dexamethasone compared with thalidomide plus dexamethasone as induction therapy before, and consolidation therapy after, double autologous stem-cell transplantation in newly diagnosed multiple myeloma: a randomized phase 3 study. Lancet. 2010;376:2075-2085.
Moreau P, Avet-Loisseau H, Facon T, et al. Bortezomib plus dexamethasone versus reduceddose bortezomib, thalidomide plus dexamethasone as induction treatment prior to autologous stem cell transplantation in newly diagnosed multiple myeloma. Blood. 2011;118:5752-5758.
Wang M, Giralt S, Delasalle K, Handy B, Alexanian R. Bortezomib in combination with thalidomide-dexamethasone for previously untreated multiple myeloma. Hematology. 2007;12:235-239.
Vij R, Kumar S, Zhang MJ, et al. Impact of pretransplant therapy and depth of disease response before autologous transplantation for multiple myeloma. Biol Blood Marrow Transplant. 2015;21:335-341.
Al-Ani F, Louzada M. Post- transplant consolidation plus lenalidomide maintenance vs lenalidomide maintenance alone in multiple myeloma: a systematic review. Eur J Haematol. 2017;99:479-488.
Cornell RF, D’Souza A, Kassim A, et al. Maintenance versus induction therapy choice on outcomes after autologous transplantation for multiple myeloma. Biol Blood Marrow Transplant. 2017;23:269-277.
Chakraborty R, Muchtar E, Kumar SK, et al. Impact of duration of induction therapy on survival in newly diagnosed multiple myeloma patients undergoing upfront autologous stem cell transplantation. Br J Haematol. 2018;182:71-77.
Mellor PW, Binder M, Buadi FK, et al. Time to plateau as a predictor of survival in newly diagnosed multiple myeloma. Am J Hematol. 2018;93:889-894.
Tandon N, Sidana S, Rajkumar SV, et al. Outcomes with early response to first-line treatment in patients with newly diagnosed multiple myeloma. Blood Adv. 2019;3:744-750.
Habermehl GK, Nakashima MO, Cotta CV, et al. IgA plasma cell neoplasms are characterized by poorer long-term survival and increased genomic complexity compared to IgG neoplasms. Ann Diagn Pathol. 2020;44:151449.
McCarthy PL, Owzar K, Hofmeister CC, et al. Lenalidomide after stem-cell transplantation for multiple myeloma. N Engl J Med. 2012;366:1770-1781.
Attal M, Lauwers-Cances V, Marit G, et al. Lenalidomide maintenance after stem-cell transplantation for multiple myeloma. N Engl J Med. 2012;366:1782-1791.
Palumbo A, Hajek R, Delforge M, et al. Continuous lenalidomide treatment for newly diagnosed multiple myeloma. N Engl J Med. 2012;366:1759-1769.
McCarthy PL, Holstein SA, Petrucci MT, et al. Lenalidomide maintenance after autologous stem-cell transplantation in newly diagnosed multiple myeloma: a meta-analysis. J Clin Oncol. 2017;35:3279-3289.
Stadtmauer EA, Pasquini MC, Blackwell B, et al. Autologous transplantation, consolidation, and maintenance therapy in multiple myeloma: results of the BMT CTN 0702 trial. J Clin Oncol. 2019;37:589-597.
Mateos MV, Richardson PG, Dimopoulos MA, et al. Effect of cumulative bortezomib dose on survival in multiple myeloma patients receiving bortezomib-melphalan-prednisone in the phase III VISTA study. Am J Hematol. 2015;90:314-319.
Avet-Loiseau H, Attal M, Moreau P, et al. Genetic abnormalities and survival in multiple myeloma: the experience of the Intergroupe Francophone du Myelome. Blood. 2007;109:3489-3495.