Anyone who takes care of kidney transplant patients knows how frustrating it is dealing with HLA antibodies. This includes pre-transplant HLA antibodies, which can make it harder to find a compatible donor, to post transplant antibodies which can cause injury patterns such as acute antibody mediated rejection and/ or chronic rejection. Antibodies are stubborn, persistent and almost impossible to eradicate. Existing therapies include IVIg, rituximab and more recently bortezomib and eculizumab. This years WTC introduces a couple new drugs into the playing field.
1. Tociluzumab (TCZ)
TCZ blocks both the soluble and cell bound receptor of IL-6. It is FDA approved for rheumatoid arthritis. Turns out that IL-6 is involved in B cell and plasma cell antibody production. The Cedars Sinai group showed that IL-6 was found at higher levels in patients with rejection and tissue staining for IL-6 was especially high in patients with AMR.
In their first abstract they used TCZ to aid in desensitization. They identified 10 patients who could not be transplanted after desensitization with IVIg and rituximab. Pts where then given IVIg at day 0 and 30, and TCZ day 15 then monthly for 6 months. If transplanted they received TCZ post op day 2 then monthly for 6 months. 5 patients were successfully transplanted at a median of 8 months from TCZ treatment. Donor specific antibody dropped from pre-TCZ to immediately pre transplant. After transplant no patient had AMR and DSA dropped further. Whether PRA dropped was not assessed.
In the next abstract TCZ was used as a treatment for AMR in pts who did not respond to IVIg and rituximab. Renal function stabilized in patients treated in TCZ and there was a near significant drop in DSA. They did not conduct repeat biopsies to evaluate for histologic resolution.
Notably in both these studies there were no SAEs related to study drug. Whether the drug really works to reduce HLA antibodies needs to be determined with larger controlled studies.
Post written by Dr. Vinay Nair, eAJKD Advisory Board member.