To the Editor:
In a recent article, Pestana et al. describe the 3-year outcome of the use of belatacept in recipients of extended criteria donor kidneys, the BENEFIT-EXT study (1). Although we welcome these longer term follow-up data, we feel that two important issues need to be discussed.
In the original, 1-year data of the BENEFIT and BENEFIT-EXT studies, a significant advantage regarding cardiovascular risk factors (blood pressure, serum lipids and incidence of NODAT) was observed in belatacept-treated patients, compared with cyclosporine-treated patients (2,3). The 3-year data of the BENEFIT-EXT study showed that this advantage was not sustained, while the paper on the 3-year follow-up data of the BENEFIT study did not address this issue anymore (4). The apparent lack of a sustained benefit regarding cardiovascular risk factors in belatacept-treated patients was neither discussed nor explained by the authors of this paper.
A second and more worrying problem is the incidence of posttransplant lymphoproliferative disorder (PTLD). In 2010, data of the belatacept phase II, BENEFIT and BENEFIT-EXT studies were pooled (5). This analysis showed that in these three studies 16 cases of PTLD occurred in 1425 patients (14 in 949 belatacept-treated patients, 2 in 476 cyclosporine-treated patients, Fisher exact test, p = 0.06). Fourteen of the 16 PTLD cases occurred within the first 18 months posttransplant and two occurred afterwards, one in each group. In the BENEFIT-EXT study, four cases of PTLD (3 in 359 belatacept-treated patients, 1 in 184 cyclosporine-treated patients) have occurred after 3 years of follow-up (1). At least two of those cases (in belatacept-treated patients) were not included in the pooled-data analysis. Overall, PTLD has therefore occurred in at least 16 of 949 belatacept-treated patients and in 2 of 476 cyclosporine-treated patients, p < 0.05). Because PTLD is a potentially lethal condition (7 of 9 patients in BENEFIT-EXT died of their disease) this is an important safety issue.
We feel that the balance between benefits and risks of belatacept as a substitute for cyclosporine might be less optimistic than suggested earlier, especially since the advantages with respect to cardiovascular risk factors seem to diminish with longer follow-up and the incidence of PTLD seems to increase.