Associate, Department of Hematology Oncology Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
Introduction: lsatuximab is an anti-CD38 monoclonal antibody (mAb) that improves outcomes and depth of response in patients with relapsed or refractory multiple myeloma (MM). Serum Immunofixation (IF) is referenced in the IMWG guidelines for assessing complete response (CR) in MM. Isatuximab is an IgG-κ mAb detected by IF, which interferes with interpretation of CR. To avoid this interference and assist in accurate clinical assessment and therapeutic monitoring of MM patients, the HYDRASHIFT 2/4 Isatuximab (HYDRASHIFT Isa IF assay) was developed by Sebia with Sanofi. It has been utilized in determining final CR in the IKEMA study (Lancet 2021, Blood Cancer J 2023). The HYDRASHIFT Isa IF assay, intended for use on the HYDRASYS system, was evaluated for providing accurate M-protein detection and CR assessment in MM. We used different IF systems in analyzing the sera of MM patients who are being given treatments containing Isatuximab in order to examine differences in M-protein detection ability and CR assessment.
Methods: Samples from 5 patients whose treatments included isatuximab were tested and monitored with IF on the HYDRASYS system (Sebia) using HYDRASHIFT 2/4 Isatuximab kit (Sebia) and with IF on the Epalyzer2 system (Helena). Serum FLCs and immunoglobulins (IGs) concentration were also measured.
Results: The median age of 5 patients (3 males and 2 females) was 73 years (range; 49-79). The HYDRASHIFT Isa IF assay completely removed the Isatuximab-based IgG-κ band from the gamma region and changed 2 of 5 patients on the response evaluations to CR. Three patients showed M-proteins, IgG-κ, IgG-λ, IgA-κ, and free kappa (BJP-κ) that originated from MM. One patient with serious renal impairment having high serum FLC (κ: 1585 mg/L and λ: 6.9 mg/L), was found to have an IgA-κ and two BJP-κ monoclonal bands by HYDRASHIFT Isa IF assay. In this patient, the Epalyzer2 detected only the IgG-κ from Isatuximab, an IgA band with no associated light chain, and one weak BJP-κ. During monitoring by the HYDRASHIFT Isa IF assay, one of the two CR patients had a weak IgA-κ detected, indicating disease progression. However, the Epalyzer2 couldn’t detect this IgA-κ and only detected IgG-κ originating from Isatuximab.
Conclusions: The HYDRASYS system and HYDRASHIFT Isa IF assay was shown to have high sensitivity and specificity, providing accurate CR assessment, and also correctly identified serum BJP and a small M-protein. These results suggest that the response and CR assessments of patients can differ depending on the IF system used. In the clinical practice of MM in patients being treated with isatuximab, the use of the HYDRASHIFT Isa IF assay showed good performance regarding the proper CR and M-protein interpretation. These studies suggest that a “proper” CR assessment of isatuximab-treated patients would be increased by use of HYDRASHIFT Isa IF assay.
