title: Suppression of the noninvolved pair of the myeloma isotype correlates with poor survival in newly diagnosed and relapsed/refractory patients with myeloma.
abstract: Heavy light chain (HLC) assays allow precise measurement of the monoclonal and of the noninvolved polyclonal immunoglobulins of the same isotype as the M-protein (e.g., monoclonal IgAκ and polyclonal IgAλ in case of an IgAκ myeloma), which was not possible before. The noninvolved polyclonal immunoglobulin is termed 'HLC-matched pair'. We investigated the impact of the suppression of the HLC-matched pair on outcome in 203 patients with multiple myeloma, a phenomenon that likely reflects the host's attempt to control the myeloma clone. Severe (>50%) HLC-matched pair suppression was identified in 54.5% of the 156 newly diagnosed patients and was associated with significantly shorter survival (45.4 vs. 71.9 months, P = 0.019). This correlation was statistically significant in IgG patients (46.4 vs. 105.1 months, P = 0.017), but not in patients with IgA myelomas (32.9 vs. 54.1 months, P = 0.498). At best response, HLC-matched pair suppression improved only in patients with ≥VGPR, indicating partial or complete humoral immune reconstitution during remission in those with excellent response. Severe HLC-matched pair suppression retained its prognostic impact also during follow-up after first response. In the 47 pretreated patients with relapsed/refractory disease, a similar correlation between severe HLC suppression and survival was noted (22.8 vs. not reached, P = 0.028). Suppression of the polyclonal immunoglobulins of the other isotypes than the myeloma protein correlated neither with HLC-matched pair suppression, nor with outcome. Multivariate analysis identified severe HLC-matched pair suppression as independent risk factor for shorter survival, highlighting the impact of isotype specific immune dysregulation on outcome in multiple myeloma.
authors.affiliation: Wilhelminen Cancer Research Institute, C/O Department of Medicine I, Center of Oncology, Hematology with Outpatient Department and Palliative Care, Wilheminenhospital, Vienna, Austria.
authors.forename: Heinz
authors.initials: H
authors.lastname: Ludwig
authors.affiliation: FH Campus Vienna, University of Applied Sciences, Vienna, Austria.
authors.forename: Dejan
authors.initials: D
authors.lastname: Milosavljevic
authors.affiliation: The Binding Site Group, Birmingham, United Kingdom.
authors.forename: Oscar
authors.initials: O
authors.lastname: Berlanga
authors.affiliation: Department of Medicine I, Center of Oncology, Hematology with Outpatient Department and Palliative Care, Wilheminenhospital, Vienna, Austria.
authors.forename: Niklas
authors.initials: N
authors.lastname: Zojer
authors.affiliation: Department of Laboratory Medicine, Wilhelminenhospital, Vienna, Austria.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Hübl
authors.affiliation: Wilhelminen Cancer Research Institute, C/O Department of Medicine I, Center of Oncology, Hematology with Outpatient Department and Palliative Care, Wilheminenhospital, Vienna, Austria.
authors.forename: Veronique
authors.initials: V
authors.lastname: Fritz
authors.affiliation: The Binding Site Group, Birmingham, United Kingdom.
authors.forename: Stephen
authors.initials: S
authors.lastname: Harding
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000097:blood*; D007132:Immunoglobulin Isotypes / Q000097:blood; D007147:Immunoglobulin Light Chains / Q000097:blood*; D007145:Immunoglobulin kappa-Chains / Q000097:blood; D007146:Immunoglobulin lambda-Chains / Q000097:blood; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000097:blood / Q000276:immunology* / Q000401:mortality* / Q000628:therapy; D015999:Multivariate Analysis; D009194:Myeloma Proteins / Q000032:analysis; D011379:Prognosis; D033581:Stem Cell Transplantation; D016019:Survival Analysis
chemical_list: D007143:Immunoglobulin Heavy Chains; D007132:Immunoglobulin Isotypes; D007147:Immunoglobulin Light Chains; D007145:Immunoglobulin kappa-Chains; D007146:Immunoglobulin lambda-Chains; D007166:Immunosuppressive Agents; D009194:Myeloma Proteins; C085016:multiple myeloma M-proteins