Efficacy and Safety Outcomes of Extended Criteria Donor Kidneys by Subtype: Subgroup Analysis of BENEFIT-EXT at 7 Years After Transplant

Abstract

The phase III Belatacept Evaluation of Nephroprotection and Efficacy as First‐Line Immunosuppression Trial–Extended Criteria Donors Trial (BENEFIT‐EXT) study compared more or less intensive belatacept‐based immunosuppression with cyclosporine (CsA)–based immunosuppression in recipients of extended criteria donor kidneys. In this post hoc analysis, patient outcomes were assessed according to donor kidney subtype. In total, 68.9% of patients received an expanded criteria donor kidney (United Network for Organ Sharing definition), 10.1% received a donation after cardiac death kidney, and 21.0% received a kidney with an anticipated cold ischemic time ≥24 h. Over 7 years, time to death or graft loss was similar between belatacept‐ and CsA‐based immunosuppression, regardless of donor kidney subtype. In all three donor kidney cohorts, estimated mean GFR increased over months 1–84 for belatacept‐based treatment but declined for CsA‐based treatment. The estimated differences in GFR significantly favored each belatacept‐based regimen versus the CsA‐based regimen in the three subgroups (p < 0.0001 for overall treatment effect). No differences in the safety profile of belatacept were observed by donor kidney subtype.

Efficacy and Safety of Belatacept Treatment in Renal Allograft Recipients at High Cardiovascular Risk—A Single Center Experience

“…Concerning safety and in contrast to Florman et al [13], we found that Belatacept treatment was associated with an increased incidence of severe infections in the univariate Cox regression. The most obvious differences were higher event rates of diarrhoea, urinary tract infection and sepsis.…”

“…eGFR improved with Belatacept treatment, but slightly decreased during CNI therapy and, in the multivariate analysis, Belatacept treatment was the only significant factor for the improvement of ΔeGFR. This is in line with the BENEFIT and BENEFIT-EXT studies, which also demonstrated an increase of GFR over a follow-up of seven years [12,13,14]. However, the CNI comparator cohort consisted of cyclosporine A-treated patients only, whereas our group was mainly treated with tacrolimus (68% of patients).…”

Chemotherapy and Transplantation: The Role of Immunosuppression in Malignancy and a Review of Antineoplastic Agents in Solid Organ Transplant Recipients

“…During phase II and III trials in KTRs, there were safety concerns regarding belatacept because of an observed increased incidence of PTLD . A total of 16 patients receiving belatacept developed PTLD, and seven of these cases had CNS involvement . Given these concerns, the U.S. Food and Drug Administration (FDA) approval carries a boxed warning for the risk of PTLD, especially in EBV‐seronegative patients.…”

Tratamiento de COVID-19 en receptores de trasplante renal

“…5 Sin embargo, los esquemas a base de belatacept ofrecen mejor función renal a largo plazo y mejor sobrevida del injerto a pesar de que pudieran tener mayor tasa de rechazo en el primer año. 6 En los últimos años se ha demostrado que cualquier esquema con uso de inhibidores mTOR está asociado a mayor mortalidad y menor sobrevida del injerto, por lo que sólo se recomiendan en casos muy especiales. 7 Respecto al manejo de inmunosupresión de mantenimiento durante la infección por SARS-CoV-2 ha sido muy heterogéneo, se realiza principalmente basado en opinión de expertos y traslapando la conducta que se toma frente a infecciones sistémicas graves.…”