353 - Comparison of Two Dose Regimens of Daratumumab (Anti-CD38) for Desensitization (DES) of Highly HLA Sensitized Patients

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Author Block: A. A. Vo¹, S. Chandran¹, X. Zhang², E. Huang¹, R. Vescio³, D. Oveisi³, A. Peng-Liang¹, R. Najjar¹, J. Shoji¹, C. Myers¹, N. Badash¹, M. Gillespie¹, K. Wakita¹, S. C. Jordan¹, ¹Kidney Transplant, Cedars-Sinai Medical Center, LA, CA, ²HLA Laboratory, Cedars-Sinai Medical Center, LA, CA, ³Hematology & Oncology, Cedars-Sinai Medical Center, LA, CA
*Purpose: HLA sensitized patients (HS) with cPRAs >99.9% have minimal access to kidney tx, as current DES protocols do not target HLA antibody producing plasma cells. Daratumumab (Dara), a human IgG1 (anti-CD38) monoclonal antibody, depletes antibody-producing plasma cells. However, the ideal treatment protocol for DES is unknown. Here, we compared the efficacy of Dara DES using Darzalex Faspro 1800mg SQ {4 vs. 8 doses}.
*Methods: From 9/20 to present, 22 HS patients with CPRA 94-100%, failed prior DES w. PLEX/IVIG/anti-CD20±anti-IL6, received PLEX/IVIG/Dara 1800mg SQ {G1 (N=10): weekly x4 doses vs. G2 (N=12): weekly x2; then monthly x6 (8 doses)}. Patients were monitored for HLA antibodies response, time to transplant, AEs/SAEs, graft & patient survival. Post-transplant induction was with alemtuzumab or thymoglobulin; followed by maintenance w. Tac (goal 7-9 ng/ml), MMF & pred taper.
*Results: A summary of the results are shown in Table 1. Overall, both regimens were well tolerated with minimal AEs/SAEs. Two patients in each group developed hypogammaglobulinemia requiring IVIg. 70% of patiens had cPRA 100% and 83% had previous transplants. Despite a minimal impact on MFIs of HLA antibodies, all patients in both groups were transplanted (50% G1 and 67% G2 had negative FCMX at transplant). However, time to transplant from DES was significantly less in G2 (8.8±10M G1 vs. 2.1±2.2M G2, p=0.05). The number of rejection episodes were numerically less in G2 and patient and graft survival were similar. One patient in G1 died of CNS lymphoma post-transplant and one graft loss occurred in G2. The mean eGFRs were similar at 12M post-transplant (G1: 69±17 vs G2: 78±22 cc/min/1.73m²).
*Conclusions: Use of Dara in both dose regimens allowed successful transplantation of HS patients including 70% cPRA 100% in both dosing groups. However, time to transplantation after DES was significantly reduced for G2. Importantly, no patients in G2 developed CMR which was felt to be a theoretical risk due to depletion of T_REG cells by Dara.