Unexpected Heterogeneity of Newly Diagnosed Multiple Myeloma Patients with Plasmacytomas

In multiple myeloma (MM), malignant plasma cells infiltrate the bone marrow. In some cases, plasma cells migrate out of the bone marrow creating either para-skeletal plasmacytomas (PS) or infiltrating soft tissues as extramedullary plasmacytomas (EMD). The aim of this study was to define risk groups in newly diagnosed MM (NDMM) patients with PS and EMD plasmacytomas. In total, 523 NDMM patients with PS plasmacytomas and 196 NDMM patients with EMD plasmacytomas were diagnosed in the Czech Republic between 2004 and 2021 using modern imaging methods. Patients’ data were analyzed from the Registry of Monoclonal Gammopathies of the Czech Myeloma Group. In NDMM patients with PS plasmacytomas, we found a subgroup with <5% of bone-marrow plasma cells to have the best prognosis (mPFS: 58.3 months (95% CI: 33.0–NA); mOS: not reached). The subgroup with >5% of bone-marrow plasma cells and ≥3 plasmacytomas had the worst prognosis (mPFS: 19.3 months (95% CI: 13.4–28.8), p < 0.001; mOS: 27.9 months (95% CI: 19.3–67.8), p < 0.001). Our results show association between tumor burden and prognosis of NDMM patients with plasmacytomas. In the case of PS plasmacytomas, NDMM patients with low BM PC infiltration have an excellent prognosis.

[1]  M. Beksac,et al.  Extramedullary disease in multiple myeloma: a systematic literature review , 2022, Blood Cancer Journal.

[2]  S. Ševčíková,et al.  Proteomic analysis of the bone marrow microenvironment in extramedullary multiple myeloma patients. , 2022, Neoplasma.

[3]  S. Ševčíková,et al.  Identification of patients at high risk of secondary extramedullary multiple myeloma development , 2021, British journal of haematology.

[4]  Shaji K. Kumar,et al.  Extramedullary disease in multiple myeloma , 2021, Blood Cancer Journal.

[5]  B. Paiva,et al.  Roadmap to cure multiple myeloma. , 2021, Cancer treatment reviews.

[6]  M. Dimopoulos,et al.  Prognostic value of minimal residual disease negativity in myeloma: combined analysis of POLLUX, CASTOR, ALCYONE, MAIA. , 2021, Blood.

[7]  S. Ševčíková,et al.  Limited efficacy of daratumumab in multiple myeloma with extramedullary disease , 2021, Leukemia.

[8]  Z. Cai,et al.  Multiple Extramedullary-Bone Related and/or Extramedullary Extraosseous Are Independent Poor Prognostic Factors in Patients With Newly Diagnosed Multiple Myeloma , 2021, Frontiers in Oncology.

[9]  M. Beksac,et al.  Expert review on soft‐tissue plasmacytomas in multiple myeloma: definition, disease assessment and treatment considerations , 2021, British journal of haematology.

[10]  P. Sonneveld,et al.  Standardization of 18F-FDG-PET/CT According to Deauville Criteria for Metabolic Complete Response Definition in Newly Diagnosed Multiple Myeloma. , 2020, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[11]  D. Dingli,et al.  Cytogenetic abnormalities in multiple myeloma: association with disease characteristics and treatment response , 2020, Blood Cancer Journal.

[12]  Andre H Crepaldi,et al.  Overall survival with daratumumab, bortezomib, melphalan, and prednisone in newly diagnosed multiple myeloma (ALCYONE): a randomised, open-label, phase 3 trial , 2019, The Lancet.

[13]  P. Sonneveld,et al.  Carfilzomib with immunomodulatory drugs for the treatment of newly diagnosed multiple myeloma , 2019, Leukemia.

[14]  N. Kröger,et al.  Tandem autologous stem cell transplantation improves outcome in newly diagnosed multiple myeloma with extramedullary disease and high-risk cytogenetics: a study from the Chronic Malignancies Working Party of EBMT. , 2019, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[15]  M. Dimopoulos,et al.  A real world multicenter retrospective study on extramedullary disease from Balkan Myeloma Study Group and Barcelona University: analysis of parameters that improve outcome , 2019, Haematologica.

[16]  S. Ševčíková,et al.  Extramedullary disease in multiple myeloma - controversies and future directions. , 2019, Blood reviews.

[17]  P. Sonneveld,et al.  Outcome of paraosseous extra-medullary disease in newly diagnosed multiple myeloma patients treated with new drugs , 2019, Haematologica.

[18]  H. Goldschmidt,et al.  Daratumumab plus Lenalidomide and Dexamethasone for Untreated Myeloma. , 2019, The New England journal of medicine.

[19]  J. Burke,et al.  Daratumumab, bortezomib, cyclophosphamide and dexamethasone in newly diagnosed and relapsed multiple myeloma: LYRA study , 2019, British journal of haematology.

[20]  N. Kröger,et al.  Impact of extramedullary disease in patients with newly diagnosed multiple myeloma undergoing autologous stem cell transplantation: a study from the Chronic Malignancies Working Party of the EBMT , 2018, Haematologica.

[21]  L. Dušek,et al.  Epidemiology of Multiple Myeloma in the Czech Republic. , 2017, Klinicka onkologie : casopis Ceske a Slovenske onkologicke spolecnosti.

[22]  G. Morgan,et al.  Haematological cancer: Where are we now with the treatment of multiple myeloma? , 2017, Nature Reviews Clinical Oncology.

[23]  S. Ševčíková,et al.  Cytogenetics in multiple myeloma patients progressing into extramedullary disease , 2016, European journal of haematology.

[24]  H. Goldschmidt,et al.  Treatment of multiple myeloma with high-risk cytogenetics: a consensus of the International Myeloma Working Group. , 2016, Blood.

[25]  N. Munshi,et al.  Development of extramedullary myeloma in the era of novel agents: no evidence of increased risk with lenalidomide–bortezomib combinations , 2015, British journal of haematology.

[26]  P. Liu,et al.  Extramedullary Manifestation in Multiple Myeloma Bears High Incidence of Poor Cytogenetic Aberration and Novel Agents Resistance , 2015, BioMed research international.

[27]  N. Munshi,et al.  Incidence and clinical features of extramedullary multiple myeloma in patients who underwent stem cell transplantation , 2014, British journal of haematology.

[28]  Hans Erik Johnsen,et al.  International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. , 2014, The Lancet. Oncology.

[29]  S. Jagannath,et al.  Patients with newly diagnosed multiple myeloma and chromosome 1 amplification have poor outcomes despite the use of novel triplet regimens , 2014, American journal of hematology.

[30]  S. Ševčíková,et al.  Soft-tissue extramedullary multiple myeloma prognosis is significantly worse in comparison to bone-related extramedullary relapse , 2014, Haematologica.

[31]  M. Terol,et al.  A multiparameter flow cytometry immunophenotypic algorithm for the identification of newly diagnosed symptomatic myeloma with an MGUS-like signature and long-term disease control , 2013, Leukemia.

[32]  B. Barlogie,et al.  Extramedullary disease portends poor prognosis in multiple myeloma and is over-represented in high-risk disease even in the era of novel agents , 2012, Haematologica.

[33]  A. Dispenzieri,et al.  Incidence of extramedullary disease in patients with multiple myeloma in the era of novel therapy, and the activity of pomalidomide on extramedullary myeloma , 2011, Leukemia.

[34]  F. Berrino,et al.  Incidence of hematologic malignancies in Europe by morphologic subtype: results of the HAEMACARE project. , 2010, Blood.

[35]  C. Pascutto,et al.  Incidence, presenting features and outcome of extramedullary disease in multiple myeloma: a longitudinal study on 1003 consecutive patients. , 2010, Annals of oncology : official journal of the European Society for Medical Oncology.

[36]  G. Morgan,et al.  The impact of extramedullary disease at presentation on the outcome of myeloma , 2009, Leukemia & lymphoma.

[37]  B. Durie The role of anatomic and functional staging in myeloma: description of Durie/Salmon plus staging system. , 2006, European journal of cancer.

[38]  J. Rossi,et al.  A Prospective, Randomized Trial of Autologous Bone Marrow Transplantation and Chemotherapy in Multiple Myeloma , 1996 .

[39]  P. Sonneveld,et al.  Multiple myeloma , 2017, Nature Reviews Disease Primers.

[40]  R Core Team,et al.  R: A language and environment for statistical computing. , 2014 .

[41]  J. Rossi,et al.  A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. Intergroupe Français du Myélome. , 1996, The New England journal of medicine.

[42]  O. Cope,et al.  Multiple myeloma. , 1948, The New England journal of medicine.