Immune Signatures Associated With Clonal Isotype Switch After Autologous Stem Cell Transplantation for Multiple Myeloma

Rebecca Ye, Sirisha Kundrapu, Stanton L. Gerson, James J. Driscoll, Rose Beck, Naveed Ali, Ola Landgren, Willem VanHeeckeren, George Luo, Nicolaus Kroger, Paolo Caimi, Marcos De Lima, Ehsan Malek

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)e213-e220
JournalClinical Lymphoma, Myeloma and Leukemia
Issue number5
StatePublished - May 2019
Externally publishedYes


  • Autologous stem cell transplantation
  • Clonal isotype switch
  • Immune reconstitution
  • Multiple myeloma
  • Myeloma microenvironment

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research


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