Rebecca Ye1, Sirisha Kundrapu2, Stanton L Gerson3, James J Driscoll4, Rose Beck2, Naveed Ali5, Ola Landgren6, Willem VanHeeckeren7, George Luo8, Nicolaus Kroger9, Paolo Caimi10, Marcos De Lima10, Ehsan Malek11. 1. Department of Medicine, New York University School of Medicine, New York, NY. 2. Department of Pathology, University Hospitals Cleveland Medical Center, Cleveland, OH. 3. Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH. 4. Division of Hematology and Oncology, The Vontz Center for Molecular Studies, University of Cincinnati College of Medicine, Cincinnati, OH. 5. Adult Hematologic Malignancies and Stem Cell Transplant Program, Seidman Cancer Center, University Hospitals Cleveland Medical Center, Cleveland, OH. 6. Myeloma Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY. 7. Division of Hematology and Oncology, University Hospital Cleveland Medical Center, Cleveland, OH. 8. Case Western Reserve University School of Medicine, Cleveland, OH. 9. Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. 10. Adult Hematologic Malignancies and Stem Cell Transplant Program, Seidman Cancer Center, University Hospitals Cleveland Medical Center, Cleveland, OH; Case Western Reserve University School of Medicine, Cleveland, OH. 11. Adult Hematologic Malignancies and Stem Cell Transplant Program, Seidman Cancer Center, University Hospitals Cleveland Medical Center, Cleveland, OH; Case Western Reserve University School of Medicine, Cleveland, OH. Electronic address: exm301@case.edu.
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.
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.