Management of interference of daratumumab with SPEP and IFE assays by using DIRA. (A) Schematic representation of DIRA for a DIRA-positive (left) and DIRA-negative case (right). (B) Example from a patient with IgG-κ M protein, who was treated with daratumumab. This patient developed a second IgG-κ band at the end of cycle 1. Response evaluation at start of cycle 16 demonstrated a decrease in M-protein from 31 to 0 g/L by SPEP analysis. Therefore, the DIRA assay was performed, which was positive, indicating that this patient had achieved a very good partial response. (C) Example from a patient with κ light chain MM, who was treated with daratumumab. This patient developed an IgG-κ band of 0 to 1 g/L at the end of the first cycle. The DIRA assay was performed at cycle 11 because of normalization of κ light chains with normal free light chain ratio. The DIRA assay was negative, which triggered bone marrow examination and showed no clonal plasma cells. Therefore, this patient had achieved stringent CR. The new IgG-κ band, which shifted after adding the anti-daratumumab antibody, represents daratumumab. anti-id, anti-idiotype.