Atypical serum immunofixation patterns frequently emerge in immunomodulatory therapy and are associated with a high degree of response in multiple myeloma

The M-protein is the major reference measure for response in multiple myeloma (MM) and its correct interpretation is key to clinical management. The emergence of oligoclonal banding is recognized as a benign finding in the postautologous stem cell transplantation setting (ASCT) for MM but its significance during non-myeloablative therapy is unknown. In a study of the immunomodulatory combination BiRD, (lenalidomide and dexamethasone with clarithromycin), we frequently detected the emergence of mono- and oligo-clonal immunoglobulins unrelated to the baseline diagnostic M-protein. The new M-proteins seen on serum immunofixation electrophoresis were clearly different in either heavy or light chain component(s) from the original M-spike protein and were termed atypical serum immunofixation patterns (ASIPs). Overall, 24/72 (33%) patients treated with BiRD developed ASIPs. Patients who developed ASIPs compared with patients treated with BiRD without ASIPs, had a significantly greater overall response (100% vs. 85%) and complete response rates (71% vs. 23%). ASIPs were not associated with new clonal plasma cells or other lymphoproliferative processes, and molecular remissions were documented. This is the first time this phenomenon has been seen with regularity in non-myeloablative therapy for MM. Analogous to the ASCT experience, ASIPs do not signal incipient disease progression, but rather herald robust response.