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Meeting report of the 7th Heidelberg Myeloma Workshop: today and tomorrow

  • M. A. BaertschEmail author
  • R. Lutz
  • M. S. Raab
  • N. Weinhold
  • H. Goldschmidt
Original Article – Cancer Research

Abstract

Purpose

The 7th Heidelberg Myeloma Workshop was held on April 5th and 6th, 2019 at the University Hospital Heidelberg.

Methods and results

Main topics of the meeting were (1) diagnostics and prognostic factors, (2) role of immunotherapy in multiple myeloma (MM), (3) current therapy of MM, (4) biology and genomics of MM as well as (5) novel treatment concepts. A debate on the status of minimal residual disease (MRD) driven therapy was held.

Conclusion

Diagnostics and treatment of newly diagnosed and relapsed MM are continuously evolving. While advances in the field of (single cell) genetic analysis now allow for characterization of the disease at an unprecedented resolution, immunotherapeutic approaches and MRD testing are at the forefront of the current clinical trial landscape.

Keywords

Multiple myeloma Minimal residual disease Immunotherapy Single-cell sequencing 

Notes

Acknowledgements

We thank all speakers and participants for their attendance and valuable input at the workshop. Moreover, we thank Annette Hluzek and Andrea Illgner for assistance with organization of the workshop and all sponsors and exhibitors for their support: Abbvie, Adaptive Biotechnologies, Amgen, Bristol-Myers Squibb, Celgene, Chugai, Janssen-Cilag, Molecular Partners, Sanofi-Aventis, Sebia, Takeda and The Binding Site.

Compliance with ethical standards

Conflict of interest

MAB: Takeda: Consultancy; Novartis: Consultancy, Research Funding; Celgene, Amgen, Janssen: Travel grants. RL: Janssen: Travel grants. MSR: Celgene: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding. NW: No conflict. HG: Amgen: Consultancy, Research Funding; Novartis: Honoraria, Research Funding; ArtTempi: Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Research Funding; Mundipharma: Research Funding; Takeda: Consultancy, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Bristol Myers Squibb: Consultancy, Honoraria, Research Funding; Adaptive Biotechnology: Consultancy; Chugai: Honoraria, Research Funding.

References

  1. Baertsch M-A, Schlenzka J, Christina H et al (2018) Subgroup analyses of the randomized GMMG phase III multicenter trial relapse suggest survival benefit of salvage autologous transplant primarily in low risk multiple myeloma. Blood 132(Suppl 1):254Google Scholar
  2. Bailly C, Leforestier R, Jamet B et al (2017) PET imaging for initial staging and therapy assessment in multiple myeloma patients. Int J Mol Sci 18(2):445CrossRefPubMedCentralGoogle Scholar
  3. Cavo M, Gay FM, Patriarca F et al (2017) 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 130(Suppl 1):401Google Scholar
  4. Cavo M, Goldschmidt H, Rosinol L et al (2018) 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 132(Suppl 1):124Google Scholar
  5. Dimopoulos MA, Oriol A, Nahi H et al (2016a) Daratumumab, lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med 375(14):1319–1331CrossRefGoogle Scholar
  6. Dimopoulos MA, Sonneveld P, Leung N et al (2016b) International myeloma working group recommendations for the diagnosis and management of myeloma-related renal impairment. J Clin Oncol 34:1544–1557CrossRefPubMedGoogle Scholar
  7. Dimopoulos MA, Dytfeld D, Grosicki S et al (2018a) Elotuzumab plus pomalidomide and dexamethasone for multiple myeloma. N Engl J Med 379(19):1811–1822CrossRefGoogle Scholar
  8. Dimopoulos MA, San-Miguel J, Belch A et al (2018b) Daratumumab plus lenalidomide and dexamethasone versus lenalidomide and dexamethasone in relapsed or refractory multiple myeloma: updated analysis of POLLUX. Haematologica 103(12):2088–2096CrossRefPubMedPubMedCentralGoogle Scholar
  9. Dimopoulos MA, Mateos M-V, Cavo M et al (2018c) One-year update of a phase 3 randomized study of daratumumab plus bortezomib, melphalan, and prednisone (D-VMP) versus bortezomib, melphalan, and prednisone (VMP) in patients (Pts) with transplant-ineligible newly diagnosed multiple myeloma (NDMM): Alcyon. Blood 132(Suppl 1):156Google Scholar
  10. Dittrich T, Benner A, Kimmich C et al (2019) Performance analysis of AL amyloidosis cardiac biomarker staging systems with special focus on renal failure and atrial arrhythmia. Haematologica 104(7):1451–1459CrossRefPubMedPubMedCentralGoogle Scholar
  11. Facon T, Kumar SK, Plesner T et al (2018) Phase 3 randomized study of daratumumab plus lenalidomide and dexamethasone (D-Rd) versus lenalidomide and dexamethasone (Rd) in patients with newly diagnosed multiple myeloma (NDMM) ineligible for transplant (MAIA). Blood 132(Suppl 1): LBA-2Google Scholar
  12. Gertz MA (2018) Immunoglobulin light chain amyloidosis: 2018 update on diagnosis, prognosis, and treatment. Am J Hematol 93(9):1169–1180CrossRefPubMedGoogle Scholar
  13. Goldschmidt H, Mai EK, Dürig J et al (2017) Response-adapted lenalidomide maintenance in newly diagnosed, transplant-eligible multiple myeloma: results from the multicenter phase III GMMG-MM5 trial. Blood 130(Suppl 1):400Google Scholar
  14. Goldschmidt H, Baertsch M-A, Schlenzka J et al (2018) Salvage autologous transplant and lenalidomide maintenance versus continuous lenalidomide/dexamethasone for relapsed multiple myeloma: results of the randomized GMMG phase III multicenter trial relapse. Blood 132(Suppl 1):253Google Scholar
  15. Guo G, Raje NS, Seifer C et al (2018) Genomic discovery and clonal tracking in multiple myeloma by cell-free DNA sequencing. Leukemia 32(8):1838–1841CrossRefPubMedPubMedCentralGoogle Scholar
  16. Hillengass J, Usmani S, Rajkumar SV et al (2019) International myeloma working group consensus recommendations on imaging in monoclonal plasma cell disorders. Lancet Oncol 20(6):e302–e312CrossRefPubMedGoogle Scholar
  17. Kumar S, Paiva B, Anderson KC et al (2016) International myeloma working group consensus criteria for response and minimal residual disease assessment in multiple myeloma. Lancet Oncol 17(8):e328–e346CrossRefPubMedGoogle Scholar
  18. Kumar SK, Callander NS, Alsina M et al (2018) NCCN guidelines insights: multiple myeloma, version 3.2018. J Natl Compr Cancer Netw 16(1):11–20CrossRefGoogle Scholar
  19. Lakshman A, Rajkumar SV, Buadi FK et al (2018) Risk stratification of smoldering multiple myeloma incorporating revised IMWG diagnostic criteria. Blood Cancer J 8(6):59CrossRefPubMedPubMedCentralGoogle Scholar
  20. Lohr JG, Kim S, Gould J et al (2016) Genetic interrogation of circulating multiple myeloma cells at single-cell resolution. Sci Transl Med 8(363):363ra147CrossRefPubMedPubMedCentralGoogle Scholar
  21. Manier S, Park J, Capelletti M et al (2018) Whole-exome sequencing of cell-free DNA and circulating tumor cells in multiple myeloma. Nat Commun 9(1):1691CrossRefPubMedPubMedCentralGoogle Scholar
  22. Mateos M-V, Dimopoulos MA, Cavo M et al (2017) Phase 3 randomized study of daratumumab plus bortezomib, melphalan, and prednisone (D-VMP) versus bortezomib, melphalan, and prednisone (VMP) in newly diagnosed multiple myeloma (NDMM) patients (Pts) ineligible for transplant (ALCYONE). Blood 130(Suppl 1): LBA-4 (SH Late Breaking Abstract #4)Google Scholar
  23. Mishima Y, Paiva B, Shi J et al (2017) The Mutational landscape of circulating tumor cells in multiple myeloma. Cell Rep 19(1):218–224CrossRefPubMedPubMedCentralGoogle Scholar
  24. Moreau P, San-Miguel J, Sonneveld P et al (2017) Multiple myeloma: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 28(suppl 4):iv52–iv61CrossRefGoogle Scholar
  25. Moreau P, Mateos M-V, Berenson JR et al (2018) Once weekly versus twice weekly carfilzomib dosing in patients with relapsed and refractory multiple myeloma (A.R.R.O.W.): interim analysis results of a randomised, phase 3 study. Lancet Oncol 19(7):953–964CrossRefGoogle Scholar
  26. Moreau P, Attal M, Hulin C et al (2019) 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 394:29–38CrossRefPubMedGoogle Scholar
  27. Munshi NC, Avet-Loiseau H, Rawstron AC et al (2017) Association of minimal residual disease with superior survival outcomes in patients with multiple myeloma. JAMA Oncol 3(1):28CrossRefPubMedPubMedCentralGoogle Scholar
  28. Neri P, Bahlis NJ, Lonial S (2016) New strategies in multiple myeloma: immunotherapy as a novel approach to treat patients with multiple myeloma. Clin Cancer Res 22(24):5959–5965CrossRefPubMedGoogle Scholar
  29. Palumbo A, Rajkumar SV, San Miguel JF et al (2014) International myeloma working group consensus statement for the management, treatment, and supportive care of patients with myeloma not eligible for standard autologous stem-cell transplantation. J Clin Oncol 32(6):587–600CrossRefPubMedPubMedCentralGoogle Scholar
  30. Palumbo A, Avet-Loiseau H, Oliva S et al (2015) Revised international staging system for multiple myeloma: a report from international myeloma working group. J Clin Oncol 33(26):2863–2869CrossRefPubMedPubMedCentralGoogle Scholar
  31. Papatzimas JW, Gorobets E, Maity R et al (2019) From inhibition to degradation: targeting the antiapoptotic protein myeloid cell leukemia 1 (MCL1). J Med Chem 62:5522–5540CrossRefPubMedGoogle Scholar
  32. Perrot A, Lauwers-Cances V, Corre J et al (2018) Minimal residual disease negativity using deep sequencing is a major prognostic factor in multiple myeloma. Blood 132(23):2456–2464CrossRefGoogle Scholar
  33. Perrot A, Lauwers-Cances V, Tournay E et al (2019) Development and validation of a cytogenetic prognostic index predicting survival in multiple myeloma. J Clin Oncol 37(19):1657–1665CrossRefPubMedGoogle Scholar
  34. Radamaker L, Lin YH, Annamalai K et al (2019) Cryo-EM structure of a light chain-derived amyloid fibril from a patient with systemic AL amyloidosis. Nat Commun 10:1103CrossRefPubMedPubMedCentralGoogle Scholar
  35. Raje N, Berdeja J, Lin Y et al (2019) Anti-BCMA CAR T cell therapy bb2121 in relapsed or refractory multiple myeloma. N Engl J Med 380:1726–1737CrossRefPubMedGoogle Scholar
  36. Rasche L, Angtuaco E, McDonald JE et al (2017a) Low expression of hexokinase-2 is associated with false-negative FDG–positron emission tomography in multiple myeloma. Blood 130(1):30–34CrossRefPubMedPubMedCentralGoogle Scholar
  37. Rasche L, Chavan SS, Stephens OW et al (2017b) Spatial genomic heterogeneity in multiple myeloma revealed by multi-region sequencing. Nat Commun 8(1):268CrossRefPubMedPubMedCentralGoogle Scholar
  38. Rasche L, Angtuaco EJ, Alpe TL et al (2018) The presence of large focal lesions is a strong independent prognostic factor in multiple myeloma. Blood 132(1):59–66CrossRefPubMedPubMedCentralGoogle Scholar
  39. Rawstron AC, Gregory WM, de Tute RM et al (2015) Minimal residual disease in myeloma by flow cytometry: independent prediction of survival benefit per log reduction. Blood 125(12):1932–1935CrossRefPubMedPubMedCentralGoogle Scholar
  40. Richardson PG, Oriol A, Beksac M et al (2019) Pomalidomide, bortezomib, and dexamethasone for patients with relapsed or refractory multiple myeloma previously treated with lenalidomide (OPTIMISMM): a randomised, open-label, phase 3 trial. Lancet Oncol 20(6):781–794CrossRefPubMedGoogle Scholar
  41. Rosinol L, Oriol A, Rios R et al (2017) Bortezomib, lenalidomide and dexamethasone (VRD-GEM) as induction therapy prior autologous stem cell transplantation (ASCT) in multiple myeloma (MM): results of a prospective phase III pethema/GEM trial. Blood 130(Suppl 1):2017Google Scholar
  42. Salwender H, Bertsch U, Weisel K et al (2019) Rationale and design of the German-speaking myeloma multicenter group (GMMG) trial HD6: a randomized phase III trial on the effect of elotuzumab in VRD induction/consolidation and lenalidomide maintenance in patients with newly diagnosed myeloma. BMC Cancer 18:504CrossRefGoogle Scholar
  43. Sanoja-Flores L, Flores-Montero J, Garcés JJ et al (2018) Next generation flow for minimally-invasive blood characterization of MGUS and multiple myeloma at diagnosis based on circulating tumor plasma cells (CTPC). Blood Cancer J 8(12):117CrossRefPubMedPubMedCentralGoogle Scholar
  44. Sobh M, Michallet M, Gahrton G et al (2016) Allogeneic hematopoietic cell transplantation for multiple myeloma in Europe: trends and outcomes over 25 years: a study by the EBMT Chronic Malignancies Working Party. Leukemia 30(10):2047–2054CrossRefPubMedGoogle Scholar
  45. Sonneveld P, Avet-Loiseau H, Lonial S et al (2016) Treatment of multiple myeloma with high-risk cytogenetics: a consensus of the international myeloma working group. Blood 127(24):2955–2962CrossRefPubMedPubMedCentralGoogle Scholar
  46. Spencer A, Lentzsch S, Weisel K et al (2018) Daratumumab plus bortezomib and dexamethasone versus bortezomib and dexamethasone in relapsed or refractory multiple myeloma: updated analysis of CASTOR. Haematologica 103(12):2079–2087CrossRefPubMedPubMedCentralGoogle Scholar
  47. Stadtmauer EA, Pasquini MC, Blackwell B et al (2019) Autologous transplantation, consolidation, and maintenance therapy in multiple myeloma: results of the BMT CTN 0702 trial. J Clin Oncol 37(7):589–597CrossRefPubMedPubMedCentralGoogle Scholar
  48. Susanibar Adaniya SP, Cohen AD, Garfall AL (2019) Chimeric antigen receptor T cell immunotherapy for multiple myeloma: a review of current data and potential clinical applications. Am J Hematol 94(S1):S28–S33CrossRefPubMedGoogle Scholar
  49. Thakurta A, Ortiz M, Blecua P et al (2019) High sub-clonal fraction of 17p deletion is associated with poor prognosis in multiple myeloma. Blood.  https://doi.org/10.1182/blood-2018-10-880831 CrossRefPubMedPubMedCentralGoogle Scholar
  50. van de Donk NWCJ, Richardson PG, Malavasi F (2017) CD38 antibodies in multiple myeloma: back to the future. Blood.  https://doi.org/10.1182/blood-2017-06-740944 CrossRefPubMedGoogle Scholar
  51. Vaxman I, Sidiqi MH, Gertz M (2018) Venetoclax for the treatment of multiple myeloma. Expert Rev Hematol 11(12):915–920CrossRefPubMedGoogle Scholar
  52. Weisel KC, Scheid C, Zago M et al (2019) Addition of cyclophosphamide on insufficient response to pomalidomide and dexamethasone: results of the phase II PERSPECTIVE multiple myeloma trial. Blood Cancer J 9(4):45CrossRefPubMedPubMedCentralGoogle Scholar
  53. Zhao W-H, Liu J, Wang B-Y et al (2018) Updated analysis of a phase 1, open-label study of LCAR-B38M, a chimeric antigen receptor T cell therapy directed against B Cell maturation antigen, in patients with relapsed/refractory multiple myeloma. Blood 132(Suppl 1):955Google Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Hematology, Oncology and RheumatologyUniversity Hospital HeidelbergHeidelbergGermany
  2. 2.Clinical Cooperation Unit Molecular Hematology/OncologyGerman Cancer Research CenterHeidelbergGermany
  3. 3.National Center for Tumor DiseasesHeidelberg University HospitalHeidelbergGermany

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