Immune signatures associated with clonal isotype switch after autologous stem cell transplantation for multiple myeloma Journal Article


Authors: Ye, R.; Kundrapu, S.; Gerson, S. L.; Driscoll, J. J.; Beck, R.; Ali, N.; Landgren, O.; VanHeeckeren, W.; Luo, G.; Kroger, N.; Caimi, P.; De Lima, M.; Malek, E.
Article Title: Immune signatures associated with clonal isotype switch after autologous stem cell transplantation for multiple myeloma
Abstract: Background: High-dose chemotherapy and autologous stem cell transplantation (ASCT) are integral components of the overall treatment for patients with multiple myeloma (MM) aged ≤ 65 years. The emergence of oligoclonal immunoglobulin bands (ie, immunoglobulins differing from those originally identified at diagnosis [termed clonal isotype switch (CIS)]) has been reported in patients with MM after high-dose chemotherapy followed by autologous stem cell transplantation. However, the clinical relevance and the correlation with immune reconstitution remains unclear. Patients and Methods: Patients with MM who had undergone ASCT from 2007 to 2016 were included in the present study. The percentage of natural killer cells, B-cells, and T-cells was measured using flow cytometry in pre- and post-ASCT bone marrow samples. CIS was defined as the appearance of a new serum monoclonal spike on serum protein electrophoresis and immunofixation that differed from original heavy or light chain detected at diagnosis. Results: A retrospective analysis of 177 patients with MM who had undergone ASCT detected CIS in 39 (22%). CIS after ASCT correlated with improved progression-free survival (52.2 vs. 36.6 months; P = .21) and overall survival (75.1 vs. 65.4 months; P = .021). Patients with a relapse had an isotype that differed from a CIS, confirming the benign nature of this phenomenon. CIS was also associated with lower CD8 T-cell percentages and a greater CD4/CD8 ratio (2.8 vs. 0.2; P = .001) compared with patients who did not demonstrate a CIS, suggestive of more profound T-cell immune reconstitution in this group. Conclusion: Taken together, our data have demonstrated that a CIS is a benign phenomenon and correlates with a reduced disease burden and enriched immune repertoire beyond the B-cell compartment. A retrospective analysis of 177 patients with multiple myeloma undergoing autologous stem cell transplant found that 22% developed new and small concentrations of monoclonal protein after transplant that differed from that originally identified at diagnosis. This phenomenon had a benign nature and correlated with improved survival and more robust bone marrow immune reconstitution beyond the B-cell compartment. © 2019 Elsevier Inc.
Keywords: adult; controlled study; human tissue; human cell; major clinical study; overall survival; flow cytometry; cd8+ t lymphocyte; progression free survival; multiple myeloma; cohort analysis; relapse; hemoglobin; melphalan; autologous stem cell transplantation; hemoglobin blood level; light chain; retrospective study; b lymphocyte; albumin; bone marrow biopsy; natural killer cell; cell clone; immunoglobulin kappa chain; immunoglobulin blood level; plerixafor; lymphocyte count; amifostine; electrophoresis; colony forming unit gm; filgrastim; immunoglobulin a; immune reconstitution; cell cloning; apheresis; albumin blood level; cd4 cd8 ratio; human; male; female; article; immunoglobulin d; clonal isotype switch; myeloma microenvironment
Journal Title: Clinical Lymphoma, Myeloma and Leukemia
Volume: 19
Issue: 5
ISSN: 2152-2650
Publisher: Elsevier Inc.  
Date Published: 2019-05-01
Start Page: e213
End Page: e220
Language: English
DOI: 10.1016/j.clml.2018.12.022
PUBMED: 30878316
PROVIDER: scopus
PMCID: PMC7444684
DOI/URL:
Notes: Source: Scopus
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  1. Carl Ola Landgren
    336 Landgren