Natural history and prognostic impact of oligoclonal humoral response in patients with multiple myeloma after autologous stem cell transplantation: long-term results from a single institution

Abstract

The emergence of an oligoclonal humoral response, resulting in the appearance of a different serum M-protein to that observed at diagnosis is a well-recognized event after autologous stem cell transplantation in multiple myeloma in complete response, and it has been considered to be a benign phenomenon. The aim of the present study was to investigate the incidence, biological characteristics and prognostic value of the oligoclonal bands in patients with myeloma who underwent autologous transplantation at our institution in the last 18 years. We proceed with a retrospective systematic review of all serum and urine immunofixation studies performed in the 211 patients with multiple myeloma who underwent melphalan-based autologous transplantation. Oligoclonal bands were observed in 34% of the patients, with a significantly higher prevalence with the use of novel agents versus conventional chemotherapy in induction (63% vs. 22%; P=0.0001). The incidence of oligoclonal bands was most frequent in non-IgG isotype, particularly in light chain only myeloma. The oligoclonal phenomenon was almost exclusive to patients in complete remission compared to other degrees of response (87% vs. 13%; P=0.0001), and lasted for a median of 1.35 years, persisting during follow up in all patients except in those who relapsed. In prognostic terms, the presence of oligoclonality resulted in a significantly longer progression-free and overall survival. Patients with oligoclonal humoral response lasting for more than one year after transplantation had a significantly longer clinical progression-free and overall survival than those with shorter duration (P=0.008 and P=0.0001, respectively), likely reflecting the importance of a robust humoral immune response.Natural history and prognostic impact of oligoclonal humoral response in patients with multiple myeloma after autologous stem cell transplantation: long-term results from a single institution

Challenges of measuring monoclonal proteins in serum

“…Further, information about isotype and electrophoretic migration position is needed when following response to therapy so that one may distinguish relapse of the original clone from the development of oligoclonal bands and/or a second (usually reactive) M-protein. Such additional M-proteins commonly occur after autologous stem cell transplants with rates as high as 73% being reported [7][8][9][10]. The development of oligoclonal bands and/or a second M-protein following autologous stem cell transplantation in MM has been reported to be a favorable prognostic sign for most patients [11].…”

Secondary monoclonal gammopathy of undetermined significance after allogeneic stem cell transplantation in multiple myeloma

“…4,9 Several studies also showed a higher frequency of sMGUS in patients treated with novel agents when compared to conventional chemotherapy. 7,16,17 Importantly, sMGUS is not a sign of relapse or progression of MM. 3,17,19,20 In fact, some studies found that patients who develop sMGUS have a superior prognosis in terms of progression-free survival (PFS) and overall survival (OS) than those without sMGUS.…”

“…7,16,17 Importantly, sMGUS is not a sign of relapse or progression of MM. 3,17,19,20 In fact, some studies found that patients who develop sMGUS have a superior prognosis in terms of progression-free survival (PFS) and overall survival (OS) than those without sMGUS. 1,2,4,6,9,10,[12][13][14]17 However, other studies, often with a small sample size, concluded that the presence of sMGUS does not relate to the prognosis of MM, or that it is only associated with a better response and not with a benefit in terms of PFS or OS.…”

“…Secondary MGUS occurs more frequently after treatment with autologous stem cell transplantation (auto-SCT) (10%-73%) [1][2][3][4][5][6][8][9][10][11][12][13][14]17 than in patients who have not undergone auto-SCT (1.6%-3.1%). 4,9 Several studies also showed a higher frequency of sMGUS in patients treated with novel agents when compared to conventional chemotherapy.…”

“…[1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] Several terms have been used to describe this phenomenon, including abnormal protein band, oligoclonal protein bands, transient mono-or oligoclonal gammopathy, apparent isotype switch, oligoclonal humoral response, atypical serum immunofixation pattern, and in myeloma patients, as we will use in this study, secondary monoclonal gammopathy of undetermined significance MGUS (sMGUS). 18 We consider post-transplant MGUS as a subtype of sMGUS.…”