Bortezomib in Kidney Transplantation

Table 1

Clinical characteristics and outcomes of published desensitization/rejection protocols using Bortezomib as combination or solo therapy.

Author (reference)	Center	N	Indication${}^1$	Complete therapy	Results Summary	Conclusions
Wahrmann et al. 2010 [18]	Vienna, Austria	2	DS	(i) 2 cycles bortezomib at intervals of 3- and 4-months, both given with steroids	(i) cPRA mildly decreased in both patients; (ii) Overall, no significant effect on the levels of antigen-specific IgG or ABO blood group antibodies	$-$
Walsh et al. 2010 [19]	Cincinnati Ohio, USA	2	AMR	(i) 1 cycle bortezomib; (ii) ongoing plasmapheresis, rituximab, intravenous steroids; (iii) pheresis done at least 72 hours post-bortezomib	(i) Immediate significant reduction of DSA; (ii) Good allograft function at 5- and 6-months follow-up; (iii) One patient had re-elevation of DSA which responded to a second course of treatment	+
Sberro-Soussan et al. 2010 [20]	Paris, France	4	AMR${}^4$	(i) 1 cycle bortezomib (solo therapy)	(i) No effect on anti-HLA antibodies within 40 subsequent days, and at 150 days follow-up.	$-$
Raghavan et al. 2009 [31]	Houston, TX, USA	1	DS	(i) 4 cycles bortezomib, one dose rituximab, daily mycophenolate	(i) Reduced PRA (55% $\to$ 30%) and significant reduction of class I antibodies; (ii) Successful transplant with good allograft function at 6-months	+
Everly 2009 [14]	Cincinnati Ohio, USA	5	AMR	(i) 1 cycle bortezomib post treatment with “other” antihumoral therapies	(i) Median follow-up of 6.9 months. All patients had 50% reduction of DSA in 2-4 weeks.; (ii) side effects in 4 of 5 patients (gastrointestinal, hematologic)${}^3$	+
Trivedi et al. 2009 [15]	Ahmedabad, Gujarat, India	11	Elevated DSA with MFI > 1000	(i) 1 cycle bortezomib followed by 2-4 treatments plasmapheresis and steroids; (ii) 6 of 11 patients received one dose rituximab	(i) Follow-up at least 80 days post treatment. All patients had reduction in MFI within 4 weeks.; (ii) 7 of 11 patients had reappearance of anti-HLA antibodies	+/$-$
Perry et al. 2009 [16]	Rochester, MN, USA	2	AMR	(i) 1 cycle bortezomib, daily plasmapheresis and IVIG	(i) Resolution of Rejection Peak MFI 13k and 14k${}^2$ At 1-year follow-up: MFI zero at and serum creatinine 0.6 and 1.3 mg/dl	+
Idica et al. 2008 [17]	??	13	DS	Details not apparent from article	(i) 10 of 13 had significant decrease (reversal) of DSA; (ii) 100% had reduced MFI of antibodies	+

${}^1$DS: Desensitization, AMR = Antibody Mediated Rejection, DSA: Donor Specific Antibodies (elevated antibodies, but no clinical rejection). ${}^2$MFI: Mean Fluorescence Index. ${}^3$Side effects mentioned include thrombocytopenia and gastrointestinal toxicities. ${}^4$Patients had subclinical antibody mediated injuries with persistent DSA; hence it was acceptable to use bortezomib as solo therapy.