Abstract
Still, many physicians give 4 cycles of combination therapy to multiple myeloma patients prior to collection of stem cells for autologous bone marrow transplant. This tradition originates from older doxorubicin-containing regiments which limited the number of cycles due to cumulative cardiotoxicity. Using older regiments, most patients had residual myeloma cells in their autologous stem-cell grafts during collection. Emerging data show that newly diagnosed multiple myeloma patients treated with modern carfilzomib/lenalidomide/dexamethasone (KRd) therapy, on average, take 6 cycles until reaching minimal residual disease (MRD) negativity. We assessed newly diagnosed patients treated with KRd focusing MRD status both in the individual patient’s bone marrow, and the corresponding autologous hematopoietic progenitor cell grafts during collection. Per protocol, stem-cell collection was allowed after 4 to 8 cycles of KRd. We found similar stem-cell yield independent of the number of cycles of KRd. At stem-cell collection, 11/30 patients (36.6%) were MRD negative in their bone marrow; all 11 patients had MRD negative hematopoietic progenitor cell grafts. Furthermore, 18/19 patients who were MRD positive in their bone marrows also had MRD negative hematopoietic progenitor cell grafts. These observations support 6 cycles of KRd as an efficacious and safe induction strategy prior to stem-cell collection.
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Acknowledgements
We thank all of the patients who contributed to this study, as well as the clinical and research staff at the Intramural Program at the National Cancer Institute, National Institutes of Health. Carfilzomib and lenalidomide, as well as funding for parts of the correlative assays for the study, were provided by Amgen and Celgene to the National Cancer Institute of the National Institutes of Health as part of a cooperative research and development agreement. The study was supported by the Intramural Program at the National Cancer Institute, National Institutes of Health; and Memorial Sloan Kettering Core Grant, Core Grant (P30 CA008748) for grant support of this work.
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Amgen and Celgene had no role in the design and conduct of the study; the collection, management, analysis, and interpretation of the data; approval of the manuscript; and decision to submit the manuscript for publication.
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Dr. Landgren has given scientific talks at meetings supported by unrestricted grants from Amgen, Celgene, Takeda, BMS, Janssen, and Merck; he has served on Independent Data Monitoring Committees (IDMCs) for clinical trials led by Janssen, Takeda, and Merck; also he has served as the Chairman for Medscape Myeloma Program. The authors declare that they have no conflict of interest.
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Tageja, N., Korde, N., Kazandjian, D. et al. Combination therapy with carfilzomib, lenalidomide and dexamethasone (KRd) results in an unprecedented purity of the stem cell graft in newly diagnosed patients with myeloma. Bone Marrow Transplant 53, 1445–1449 (2018). https://doi.org/10.1038/s41409-018-0170-0
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DOI: https://doi.org/10.1038/s41409-018-0170-0
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