Oligoclonal Bands In Patients with Multiple Myeloma In Complete Remission After Induction Chemotherapy: Strong Association with the Use of Novel Agents

The emergence of oligoclonal bands is a well recognized event after autologous stem cell transplantation in multiple myeloma (MM). These atypical serum immunofixation (IFE) patterns are associated with good prognosis, likely due to a durable immune reconstitution. They can appear with novel immunomodulatory drugs such as lenalidomide, but its prevalence with other induction treatments has not been reported.

To determine the prevalence of serum and/or urine immunoglobulin oligoclonality in patients with MM in CR after primary therapy with cytotoxic agents or with new induction chemotherapy regimens incorporating novel drugs up-front.

Thirty-three patients (15M/18F; median age at diagnosis 59 years, range 25 to 89) with MM in CR after different induction regimens were studied. Initial baseline demographics, clinical and laboratory data, treatment and follow-up were collected. An oligoclonal band was defined as the presence of a serum and/or urine IFE monoclonal spike different either in heavy and/or light chain component from the original myeloma protein.

The initial clinical and laboratory findings as well as the induction treatments are shown in the table 1. Eighteen patients (54.5%) received induction with conventional chemotherapy and 15 (45.5%) with novel agents. In the latter group, the induction regimen was based on combinations of glucocorticoids with lenalidomide (26.7%), thalidomide (26.7%), bortezomib (33.3%) or bortezomib plus lenalidomide (13.3%). In the overall series, 11 out of the 33 patients (33.3%) developed an oligoclonal band. These abnormal bands observed in the IFE pattern lasted from 2.2 to 55.7 months (median 11.5 months).Four patients (36.4%) had a fluctuating oligoclonal pattern during their follow-up while the remaining showed a single oligoclonal immunoglobulin. The most frequent isotype seen in oligoclonal bands was IgG-κ (72.7%), as it was previously described after ASCT. In the group treated with cytotoxic agents, the prevalence of oligoclonal bands was observed in 2 patients (11.1%), both of them had been treated with cyclophosphamide and dexamethasone. In contrast, induction with novel drugs resulted in 9 out of 15 patients (60%) developing oligoclonal bands in serum and/or urine (chi-square test 2-sided, p=0.003). Interestingly, five patients with oligoclonal humoral response have already relapsed (45.5%). In four of them, relapse was coincident with the disappearance of the previous oligoclonality, while in the remaining case the disappearance of the oligoclonality preceded relapse in six months.

This is the first report showing a significantly different frequency of oligoclonal bands in patients with MM in CR after conventional cytotoxic therapy versus induction incorporating novel agents. This difference is likely due to a greater antimyeloma effect, a strongest immune reconstitution resulting from the effect of novel drugs, or both. With the progressive use of these drugs, the CR rate and consequently the proportion of patients who develop an oligoclonal immune response with oligoclonal bands will likely increase. However, the mechanism associated with the emergence of the oligoclonal bands as well as its prognostic impact is still unknown and deserve further investigation.

Cibeira:Janssen-Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. Rosiñol:Janssen-Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. Blade:Janssen-Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.