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MULTIPLE MYELOMA, GAMMOPATHIES

Intensifying treatment in PET-positive multiple myeloma patients after upfront autologous stem cell transplantation

Leukemia volume 37, pages 2107–2114 (2023)Cite this article

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Abstract

18F-Fluorodeoxyglucose positron emission tomography/computed tomography (PET) positivity after first-line treatment with autologous stem cell transplantation (ASCT) in multiple myeloma is strongly correlated with reduced progression-free and overall survival. However, PET-positive patients who achieve PET negativity after treatment seem to have comparable outcomes to patients who were PET negative at diagnosis. Hence, giving PET-positive patients additional treatment may improve their outcome. In this phase II study, we screened first-line patients with very good partial response (VGPR) or better after ASCT with PET. PET-positive patients received four 28-day cycles of carfilzomib-lenalidomide-dexamethasone (KRd). Flow cytometry-based minimal residual disease (MRD) analysis was performed before and after treatment for correlation with PET. Overall, 159 patients were screened with PET. A total of 53 patients (33%) were PET positive and 57% of PET-positive patients were MRD negative, demonstrating that these response assessments are complementary. KRd consolidation converted 33% of PET-positive patients into PET negativity. MRD-negative patients were more likely to convert than MRD-positive patients. In summary, PET after ASCT detected residual disease in a substantial proportion of patients in VGPR or better, even in patients who were MRD negative, and KRd consolidation treatment changed PET status in 33% of patients.

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Fig. 1: Consort diagram.
Fig. 2: PET before (upper) and after (lower) KRd treatment.
Fig. 3: Estimated mean change in global quality of life score.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request, please contact the corresponding author by e-mail: jaknoe@ous-hf.no.

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Acknowledgements

JNN is a PhD candidate at the University of Oslo. This work is submitted as partial fulfillment of the requirement of the PhD. KG Jebsen Center for B-cell malignancies granted funds for JNN’s PhD education. This trial was supported by research funding and drug supply from Amgen to FS. We want to thank all patients in the study and their relatives.

Author information

Authors and Affiliations

  1. Oslo Myeloma Center, Department of Hematology, Oslo University Hospital, Oslo, Norway

    Jakob Nordberg Nørgaard, Anna Lysén, Nora Remen & Fredrik Schjesvold

  2. Institute of Clinical Medicine, University of Oslo, Oslo, Norway

    Jakob Nordberg Nørgaard & Mona-Elisabeth R. Revheim

  3. KG Jebsen Center for B cell malignancies, University of Oslo, Oslo, Norway

    Jakob Nordberg Nørgaard, Anna Lysén & Fredrik Schjesvold

  4. Department of Hematology, Odense University Hospital, Odense, Denmark

    Niels Abildgaard

  5. Department of Clinical Research, University of Southern Denmark, Odense, Denmark

    Niels Abildgaard

  6. Division of Hematology, Haukeland University Hospital, Bergen, Norway

    Galina Tsykunova

  7. Department of Hematology, Rigshospitalet, Copenhagen, Denmark

    Annette Juul Vangsted

  8. Department of Hematology, Champalimaud Centre for the Unknown, Lisboa, Portugal

    Cristina João

  9. Nova Medical School, Universidade Nova de Lisboa, Lisbon, Portugal

    Cristina João

  10. Quality of Life Research Center, Department of Haematology, Odense University Hospital, Odense, Denmark

    Lene Kongsgaard Nielsen

  11. Department of Hematology, Gødstrup Hospital, Herning, Denmark

    Lene Kongsgaard Nielsen

  12. OPEN, Open Patient data Explorative Network, Odense University Hospital, Odense, Denmark

    Lene Kongsgaard Nielsen

  13. Department of Immunology, Oslo University Hospital, Oslo, Norway

    Liv Osnes

  14. Division for Radiology and Nuclear Medicine, Oslo University Hospital, Oslo, Norway

    Caroline Stokke, James P. Connelly & Mona-Elisabeth R. Revheim

  15. Department of Physics, University of Oslo, Oslo, Norway

    Caroline Stokke

  16. The Intervention Centre, Oslo University Hospital, Oslo, Norway

    Mona-Elisabeth R. Revheim

Authors
  1. Jakob Nordberg Nørgaard
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Consortia

Nordic Myeloma Study Group (NMSG)

  • Jakob Nordberg Nørgaard
  • , Niels Abildgaard
  • , Anna Lysén
  • , Galina Tsykunova
  • , Annette Juul Vangsted
  •  & Fredrik Schjesvold

Contributions

JNN performed research, collected data, analyzed and interpreted data, performed statistical analysis, wrote the manuscript, and approved the manuscript. NA designed research, performed research, collected data, and approved the manuscript. AL designed research, performed research, collected data, analyzed and interpreted data, and approved the manuscript. GT performed research, collected data, and approved the manuscript. AJV designed research, performed research, collected data, and approved the manuscript. CJ performed research, collected data, and approved the manuscript. NR performed research, collected data, and approved the manuscript. LKN designed the QoL substudy and collected, analyzed and interpreted data, wrote sections of the manuscript, and approved the manuscript. Henrik Eshøj designed the QoL substudy and collected, analyzed and interpreted data, and approved the manuscript. Sadly, Henrik passed away before the study was published. LO analyzed and interpreted data, wrote sections of the manuscript, and approved the manuscript. CS designed research and approved the manuscript. JPC performed research, collected data, analyzed and interpreted data, and approved the manuscript. M-ERR designed research, performed research, collected data, analyzed and interpreted data, wrote sections of the manuscript, and approved the manuscript. FS designed research, performed research, collected data, analyzed and interpreted data, performed statistical analysis, wrote the manuscript, and approved the manuscript.

Corresponding author

Correspondence to Jakob Nordberg Nørgaard.

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Competing interests

JNN has received honoraria from Janssen. NA has received research grants from Janssen, Celgene, BMS, Amgen, and Takeda. GT has received consultancy/honoraria from Amgen, Janssen, Ablynx, and Sobi, as well as research funding from Amgen. FS has received honoraria from Amgen, BMS, Abbvie, Janssen, and GSK. He has received grants from Amgen and Targovax and received compensation for adbords from GSK, Takeda, BMS, Janssen, Oncopeptides, Sanofi, and XNK therapeutics. The remaining authors declare no competing interests.

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Nørgaard, J.N., Abildgaard, N., Lysén, A. et al. Intensifying treatment in PET-positive multiple myeloma patients after upfront autologous stem cell transplantation. Leukemia 37, 2107–2114 (2023). https://doi.org/10.1038/s41375-023-01998-7

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