In Europe 40,000 new cases of Multiple Myeloma (MM) are detected each year making it the second most common blood cancer (1).
It is well known that the newer treatments for MM that use humanized monoclonal antibodies (mAbs) can interfere with the patient’s native antibodies in immunofixation tests. This can mislead the pathologist in interpreting the patient’s response to treatment. Immunofixation is one of the tests referenced in the IMWG (International Myeloma Working Group) guidelines to establish the diagnosis of complete response in a patient with multiple myeloma.
Sanofi’s Sarclisa® (isatuximab) is currently in multiple phase 3 clinical trials and received approval for use from the European commission (EC) in June 2020 for the treatment of MM. Sarclisa® is a monoclonal antibody that binds to an epitope on CD38 receptors which are highly expressed on MM cells and is believed to promote programmed tumor cell death and immunomodulatory activity. Sarclisa® is often used in conjunction with pomalidomide and dexamethasone in the treatment of relapsed and refracted MM(2). Patients with MM are often tested using Serum Protein Electrophoresis (SPE) and Immunofixation (IFE) techniques to monitor disease progression and treatment effectiveness, by the detection of monoclonal bands in the beta and gamma zones.
Any abnormal bands in the beta and gamma globulin zones are suspected to be monoclonal proteins and will need further investigation with IF. Isatuximab is a therapeutic IgG kappa antibody. It therefore, simulates a band detected by SPE and IF, mimicking an endogenous IgG Kappa paraprotein thus, leading to interference.
Sebia’s Hydrashift 2/4 isatuximab assay uses anti-isatuximab antibodies to form an anti-isatuximab-isatuximab antibody complex. The formation of this Isatuximab complex changes the charge of the molecule and therefore causes it to migrate in the alpha zone rather than the gamma zone. A positive IF result will show both the Isatuximab bands in the alpha zone of the IgG and Kappa lanes and any endogenous monoclonal bands in the gamma zone. Complete absence of monoclonal bands in the gamma zone indicates a negative result.
Having a reliable IF result is vital in the staging of MM patients and to achieve Complete Response (CR) and Stringent Complete Response (sCR)
As with Hydrashift 2/4 daratumumab, it is designed for use on Sebia’s semi-automated gel platform HYDRASYS 2. Sebia Hydrashift 2/4 isatuximab assay kit (40 tests) is ready to use on Hydrasys 2 Scan in conjunction with the Hydragel Immunofixation kit.
- João C, Costa C, Coelho I, Vergueiro MJ, Ferreira M, Silva MG. Long‐term survival in multiple myeloma. Clinical Case Reports. 2014;2(5):173-179. doi:10.1002/ccr3.76. 3. Schey SA, Morris J, Maguire Á, Dhanasiri
- Sanofi: Press Releases, Tuesday, June 2, 2020. (2021). Retrieved 24 March 2021, from https://www.sanofi.com/en/media-room/press-releases/2020/2020-06-02-12-47-38
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