Dr. Thomas Bise (Düdingen/ CH), Dr. Claudia Moskwa (Greifswald/ DE), Dr. Kathleen Selleng (Greifswald/ DE), John Hall (Emeryville, CA/ US), Colleen Brown (Emeryville, CA/ US), Dr. Dennis Yee (Emeryville, CA/ US), Dr. Jody Melton Witt (Emeryville, CA/ US), Dr. Laziza Amniai (Parets del Vallès/ ES), Ariane Caesar (Düdingen/ CH)
Background
Monoclonal antibody treatments for cancer therapy, such as daratumumab (Anti-CD38), cause panagglutination of Reagent Red Blood Cells and, thus, interfere with immunohematology (IH) testing. As previously shown (Binda et al.: 2018, Transfus Med Hemother), pre-incubation of plasma with a patented soluble CD38 (sCD38) was able to neutralize Anti-CD38 when samples were spiked with the oncological drug (Darzalex, Janssen, Horsham, USA).
Methods
To further prove efficient neutralization, sCD38 has been used to pretreat 53 patient samples (52 having received Daratumumab and 1 Isatuximab). The blood samples were collected between 0 and 245 days after the last infusion. Evaluation has been carried out with different immunohematological methods, i.e. antibody screening or crossmatching and using tube method or DG Gel technique (Medion Grifols Diagnostics, Düdingen, Switzerland; Diagnostic Grifols, Parets del Valles, Spain). Pre-treatment consisted in adding up to 4µl of sCD38 per 25µl of plasma. As none of those plasma naturally contained alloantibodies, 16 patient samples were then spiked with identified polyclonal antisera covering 13 different specificities and tested again.
Results
In 46 patients receiving Daratumumab and 1 receiving Isatuximab, sCD38 was able to completely neutralize the Anti-CD38 contained in plasma tested in the different IH methods (Table 1). Partial neutralization was observed with samples that had high Anti-CD38 titer and were collected within 28 days after last infusion (Table 2). Increasing even further the dose of sCD38 might improve the blocking of the interference. Except for Anti-Fya and Anti-Fyb, all alloantibodies namely Anti-D, -C, -c, -E, -e, -K, -Jka, -Jkb, -S, -s spiked in the patient samples could be detected with no significant loss in reaction strength. Investigation to clarify the reason for the interference with Duffy antibodies is ongoing.
Conclusion
The results of this study show that, at the doses used, sCD38 can completely neutralize Anti-CD38 in 88.7% of the patient samples. sCD38 has been designed as high affinity epitope, which makes it potentially a universal and broad solution for neutralization of any Anti-CD38. This hypothesis seems to be confirmed by the successful inhibition of Isatuximab in patient sample. In addition, as pre-treatment with sCD38 is done on plasma, different IH methods and techniques can be used afterwards.
Offenlegung Interessenkonflikt:
T. Bise, J. Hall, C. Brown, D. Yee, J. Melton Witt, L. Amniai and A. Caesar are employees of Grifols S.A.