Isatuximab Monotherapy for Desensitization in Highly Sensitized Patients Awaiting Kidney Transplant

Flavio Vincenti, Oriol Bestard, Amarpali Brar, Josep M. Cruzado, Daniel Seron, A. Osama Gaber, Nicole Ali, Anat R. Tambur, Helen Lee, Giovanni Abbadessa, Jo Anne Paul, Markus Dudek, Ruby J. Siegel, Alba Torija, Dorothée Semiond, Lucie Lépine, Nils Ternes, Robert A. Montgomery, Mark Stegall

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Background Patients with calculated panel reactive antibody (cPRA) $80.00%, particularly those with cPRA $99.90%, are considered highly sensitized and underserved by the Kidney Allocation System. Desensitization removes circulating reactive antibodies and/or suppresses antibody production to increase the chances of a negative crossmatch. CD38 is expressed highly on plasma cells, thus is a potential target for desensitization. Methods This was an open-label single-arm phase 1/2 study investigating the safety, pharmacokinetics, and preliminary efficacy of isatuximab in patients awaiting kidney transplantation. There were two cohorts, cohorts A and B, which enrolled cPRA $99.90% and 80.00% to,99.90%, respectively. Results Twenty-three patients (12 cohort A, 11 cohort B) received isatuximab 10 mg/kg weekly for 4 weeks then every 2 weeks for 8 weeks. Isatuximab was well tolerated with pharmacokinetic and pharmacodynamic profiles that indicated similar exposure to multiple myeloma trials. It resulted in decreases in CD381 plasmablasts, plasma cells, and NK cells and significant reductions in HLA-specific IgG-producing memory B cells. Overall response rate, on the basis of a predefined composite desensitization end point, was 83.3% and 81.8% in cohorts A and B. Most responders had decreases in anti-HLA antibodies that were maintained for 26 weeks after the last dose. Overall, cPRA values were minimally affected, however, with only 9/23 patients (39%) having cPRA decreases to target levels. By study cutoff (median follow-up of 68 weeks), six patients received transplant offers, of which four were accepted. Conclusions In this open-label trial, isatuximab was well tolerated and resulted in a durable decrease in anti-HLA antibodies with partial desensitization activity.

Original languageEnglish (US)
Pages (from-to)347-360
Number of pages14
JournalJournal of the American Society of Nephrology
Volume35
Issue number3
DOIs
StatePublished - Mar 1 2024

ASJC Scopus subject areas

  • Medicine(all)

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