Patients highly allosensitized against HLA antigen awaiting for a kidney transplant have less compatible transplants to them, increasing their waitlist time and mortality. Current desensitization strategies need to be improved with a high remaining acute rejection rate in this population and a substantial survival benefit which is not uniformly reported in the literature. The investigators propose to use daratumumab, a human IgG1 (Immunoglobulin Gamma-1) monoclonal antibody directed against the CD38 molecule (cluster of differentiation 38) witch induce response in refractory multiple myeloma by depleting plasma cells, as a new agent of desensitization. The study will address the hypothesis that daratumumab can lead to a significant decrease in calculated panel reactive antibodies by elimination of anti-HLA antibodies-producing plasma cells and facilitate the access to transplantation with a safety profile in highly sensitized patients registered in our kidney transplantation center.

Inclusion Criteria:

• Adults ≥ 18 years awaiting a kidney allograft transplantation
• Registration on the French National kidney allograft waiting-list for at least three years
• cPRA ≥ 95% for at least three years
• COVID-19 vaccination using Pfizer BioNtech vaccine for: Patients who have never been infected with COVID-19, inclusion at least one month after the third dose OR Patients previously infected with COVID-19 proved with PCR or serology, inclusion at least one month after the second injection of Pfizer BioNtech vaccine.
• Effective contraception up to three months after the end of treatment
• Informed consent obtained in accordance with local regulations;
• Affiliation to a social security regime.

Exclusion Criteria:

• Refusal of COVID-19 vaccination using Pfizer BioNtech vaccine
• Hypersensitivity to daratumumab or to any of the excipients),
• Known allergy to methylprednisolone and its excipients or to diphenhydramine and its excipients or to acetaminophen and its excipients or to valacyclovir and its excipients.
• Severe hepatocellular insufficiency
• Psychotic state not yet controlled by treatment
• Patient refusal
• Pregnant or breastfeeding woman or ineffective contraception
• Active neoplasia
• Active infection
• Active HBV infection, including HBsAg positive at screening
• Participation in another interventional study involving human participants or being in the exclusion period at the end of a previous study involving human participants
• Persons deprived of their liberty by judicial or administrative decision,
• Persons under legal protection/safeguard of justice,
• Patients under duress psychiatric care,
• Persons admitted to a health or social institution
• Patient on AME (state medical aid)
• Contraindication to kidney transplantation

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