Targeting CD38 to reduce anti-HLA antibody levels: A new and effective option to be integrated into desensitization protocols?

Desensitization protocols are employed in patients with antibody-mediated organ rejection or hematopoietic stem cell (HSC) transplant recipients from ´HLA-mismatched´ donors with donor-specific antibodies (DSA). However, these protocols sometimes have limitations in effectively reducing anti-HLA antibody levels and maintaining this reduction over time. As a result, there is an ongoing search for new, effective therapies to implement current protocols, involving anti-CD20, bortezomib, and plasma exchange. This case report explores the impact of daratumumab, a well-known anti-CD38 antibody used in the treatment of multiple myeloma, on a patient enrolled in a prospective observational study MyTH ("(My)eloma (T)herapy vs. Anti-(H)LA antibodies"). The patient has been treated since 2021 and follow-up data are presented here, showing a correlation between the kinetics of daratumumab administration and the MFI levels of an anti-HLA antibody against DR12 (baseline MFI of 3,890). These data support the role of anti-CD38 in reducing anti-HLA antibody synthesis.