Obinutuzumab in kidney transplantation: Past, present, and future

Table 2 Current literature on obinutuzumab use in kidney transplantation

Ref.	Year	Focus	Study design	Population	Treatment scheme	Main outcomes	IRR	SAE	FU
Redfield et al[37]	2019	Desensitization in highly sensitized KT candidates	Phase 1b, open label	25 ESRD patients (cPRA ≥ 98%); 5 received 1 OBI dose, 20 received 2 OBI doses	OBI 1 gon days 1 and 15 (± week 24) + IVIg 2 g/kg on days 22 and 43	> 90% peripheral CD19+ B-cell depletion; modest anti-HLA MFI reduction; 8/25 candidates proceeded to transplant	Mild–moderate IRRs in 52% (mainly chills, nausea, hypotension after first infusion)	44% had infections (11 SAEs in 9 patients), including pneumonia and nocardiosis	12 months
Zhang et al[72]	2021	B-cell depletion and CDC crossmatch	Observational cohort	12 sensitized KT candidates (6 OBI vs 6 RTX)	OBI 1 g vs RTX	Obinutuzumab achieved a median of 98% CD19+ B-cell reduction; CDC crossmatch results not influenced by OBI (unlike RTX)	Not reported	Not reported	2 weeks
Zhang et al[72]	2021	Lymphoid-tissue B-cell depletion	Sub study of Phase 1b trial	7 KT recipients	Same OBI + IVIg regimen as Redfield et al[37]	Significant reduction in CD20+ B-cell frequency in retroperitoneal lymph nodes vs non- OBI controls; depletion of naïve B cells, memory B cells, and plasmablasts	Not specified	Not specified	Up to 24 weeks
Favi et al[35]	2022	Induction in DEAP-HUS	Case report	1 high-risk KT recipient with CFHR1/CFHR3 deletion and anti-CFH antibody	Eculizumab 900 mgon days 0, and 30 + OBI 1 g on day 6	Complete complement blockade; rapid, full, and sustained CD20+ B-cell depletion; undetectable anti-CFH antibody; stable graft function	None	None	1 year
NasrAllah et al[38]	2022	OBI vs RTX: B-cell depletion and CDC-crossmatch	Comparative cohort	12 highly sensitized KT candidates/recipients (6 OBI, 6 RTX)	OBI 1 g or RTX 375 mg/m² with B-cell count and CDC-crossmatch assessed pre- and 2 weeks post-infusion	OBI induced a 98% median reduction in CD19+ B cells; unlike RTX, OBI did not cause false positive CDC-crossmatch	Not reported	Not reported	Not applicable
Favi et al[36]	2024	Treatment of ABMR	Case series	2 high-risk KT recipients with early active ABMR refractory to conventional therapy	Eculizumab 900 mg followed by OBI 1 g	Complement inhibition with clearance of intra-graft C4d and C5b-9 depositions; durable peripheral B-cell depletion; preformed and de novo DSA decline; preserved graft function with no signs of ABMR after 3 years	Nausea, vomiting, tachycardia,	CMV viremia, SARS-CoV2 infection, leukopenia	3 years
Ravani et al[71]	2024	Recurrent FSGS	Case series	2 KT recipients with early, RTX-resistant recurrent FSGS	OBI 1 g and DAR 16 mg/kg (two doses)	Rapid and complete remission of proteinuria; plasmapheresis discontinued; sustained albumin normalization; no further relapses	Not reported	None reported	≥ 12 months

ABMR: Antibody-mediated rejection; CDC: Complement-dependent cytotoxicity; CFHR: Complement factor H-related plasma proteins; cPRA: Calculated Panel Reactive Antibody; DAR: Daratumumab; DEAP-HUS: Deficiency of complement factor H-related plasma proteins and autoantibody positive form of hemolytic uremic syndrome; DSA: Donor-specific antibodies; ESRD: End-stage renal disease; FSGS: Focal segmental glomerulosclerosis; FU: Follow-up; KT: Kidney transplant; IRR: Infusion-related reaction; IVIg: Intravenous human polyclonal immunoglobulin; MFI: Mean fluorescence intensity; OBI: Obinutuzumab; RTX: Rituximab; SAE: Serious adverse event.