This phase 2, double-blind, randomised controlled study (BEL114424) explores the safety and potential efficacy of addition of belimumab to standard of care in renal transplantation (ClinicalTrials.gov number NCT01536379; EudraCT number 2011-006215-56).

Alloantibody production by terminally differentiated B cells negatively impacts kidney transplant outcomes but regulatory B cells may promote transplant tolerance. B Lymphocyte Stimulator (BLyS; also known as BAFF), is a cytokine that enhances B cell survival and proliferation, but to date, this pathway has not been targeted in human kidney transplant recipients.

Patients were randomised to an anti-BLyS antibody, intravenous belimumab 10mg/kg (n=14), or placebo (n=14) on the day of renal transplant and at weeks 2, 4, 8, 12, 16 and 20 in addition to standard of care immunosuppression (basiliximab, mycophenolate mofetil, tacrolimus and prednisolone).

Belimumab-treated patients had a reduction in the proportion of naïve B cells with a concomitant increase in peripheral memory B cells but reduced activated CD95+ memory B cells. On in-vitro stimulation, B cells from belimumab-treated subjects produced more interleukin-10 relative to interleukin-6, consistent with a proportional increase in regulatory B cells. A post hoc whole blood gene expression analysis found reduced expression of immunoglobulin-coding transcripts and TNFRSF17 (B-cell maturation antigen) in belimumab-treated patients, consistent with fewer circulating plasmablasts. In CD4+ T cells, a similar analysis found reduced expression of cell-cycle genes, suggesting reduced T-cell proliferation in belimumab-treated patients. Both arms had similar rates of adverse events, including infections, during 12-month follow-up.

This pilot study suggests that belimumab in combination with the above standard immunosuppression may promote a more tolerant immune phenotype by modulating both cellular and humoral alloimmunity without conferring additional risk of infection.

GlaxoSmithKline funded this study.

CITATION INFORMATION: Banham G, Flint S, Torpey N, Lyons P, Shanahan D, Gibson A, O'Sullivan A.-M, Jones R, Devey L, Richards A, Erwig L, Savage C, Smith K, Henderson R, Clatworthy M. A Phase-Two, Randomised, Placebo-Controlled Trial: Belimumab in Renal Transplantation Targets Naïve, Activated Memory and Antibody Producing B Cells Whilst Sparing Regulatory B Cells. Am J Transplant. 2017;17 (suppl 3).

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