Benefits of rituximab combined with intravenous immunoglobulin for desensitization in kidney transplant recipients.
BACKGROUND
Highly HLA-sensitized (HS) patients have difficulty accessing compatible donors, especially deceased donor (DD) transplants. Desensitization protocols (DES) have evolved, but rigorous evaluation is lacking. Here, we examined the efficacy of rituximab as a DES agent in a placebo-controlled trial.


METHODS
Candidates were randomized to IVIG+placebo versus IVIG+rituximab. End points included rates of transplantation, antibody-mediated rejection (ABMR), and renal function. Protocol biopsies were performed at 1 year and analysis of patient and graft survival and donor-specific HLA antibodies (DSA) were performed.


RESULTS
Initially, 15 HS DDs were randomized with 13 receiving transplants. However, we discontinued study entry after five serious adverse events were observed. The study was un-blinded and attribution of patients was noted (IVIG+placebo N=7, IVIG+rituximab N=6). No significant differences were seen in DSA levels at transplant. All ABMR episodes occurred in the IVIG+placebo arm and required intense therapy (P=0.06). The two graft losses were in the placebo group. DSA rebound associated with severe ABMR was seen in three patients in the IVIG+placebo group. No rebound was seen in the IVIG+rituximab group. Renal function at 6 and 12 months showed a significant benefit for IVIG+rituximab (P=0.04).


CONCLUSIONS
Based on limited assessment with acknowledged limitations, both protocols appear effective in achieving levels of DSA allowable for transplantation. However, IVIG+rituximab appeared more effective in preventing DSA rebound and, more importantly, preventing ABMR and development of transplant glomerulopathy.
1 Comprehensive Transplant Center, Transplant Immunotherapy Program, Cedars-Sinai Medical Center, Los Angeles, CA. 2 HLA Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA. 3 Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA. 4 Transplant Immunology Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA. 5 Address correspondence to: Stanley C. Jordan, M.D., David Geffen School of Medicine at UCLA and Kidney Transplant Program, Cedars-Sinai Medical Center, Los Angeles, CA 90048.
Ashley A
AA
Vo
Jua
J
Choi
Kristen
K
Cisneros
Nancy
N
Reinsmoen
Mark
M
Haas
Shili
S
Ge
Mieko
M
Toyoda
Joseph
J
Kahwaji
Alice
A
Peng
Rafael
R
Villicana
Stanley C
SC
Jordan
D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage* / Q000009:adverse effects; D003888:Desensitization, Immunologic / Q000379:methods*; D004338:Drug Combinations; D005260:Female; D006084:Graft Rejection; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage* / Q000009:adverse effects; D007518:Isoantibodies / Q000097:blood; D016030:Kidney Transplantation / Q000009:adverse effects; D008297:Male; D000069283:Rituximab; D014019:Tissue Donors
D058846:Antibodies, Monoclonal, Murine-Derived; D004338:Drug Combinations; D006680:HLA Antigens; D016756:Immunoglobulins, Intravenous; D007518:Isoantibodies; D000069283:Rituximab