Belatacept Improves Renal Function in Kidney Transplant Patients

Jim Kling

May 12, 2010

May 12, 2010 (San Diego, California) — Two new reports of 2-year outcomes with the drug belatacept show that it continues to be associated with superior renal function after kidney transplantation, compared with a regimen based on cyclosporine A (CsA). The results were presented here at the American Transplant Congress 2010.

Both studies continued the analysis of the 3-year phase 3 BENEFIT trial, which showed that patients treated with belatacept had improved renal function and similar patient and graft survival at 1 year, despite an increased incidence of acute rejection soon after transplantation.

The BENEFIT trial looked at adults receiving a kidney from a living donor or a standard criteria deceased donor. The study had three groups: a more intensive (MI) regimen of belatacept (164 patients completed treatment at 2 years); a less intensive (LI) regimen of belatacept (176 patients completed treatment at 2 years); and a CsA regimen (153 patients completed treatment at 2 years). All patients were treated with basiliximab induction, mycophenolate mofetil (MMF), and corticosteroids.

The researchers found that the superior renal function that was found at year 1 continued at the end of year 2 (as indicated by calculated glomerular filtration rate [GFR] or measured GFR, which was 15 to 17 mL/min higher in these groups, MI or LI vs CsA; P < .0001).

Eight additional patients had an acute rejection episode between year 1 and year 2 (4 patients in the MI group and 4 patients in the CsA group), and 2 cases of posttransplant lymphoproliferative disorder (PTLD) occurred in the MI group between year 1 and year 2 (total cases in BENEFIT to July 2009 were 3 with MI; 2 with LI; and 1 with CsA).

Improvements in cardiovascular and metabolic risk factors evidenced at year 1 remained at the end of year 2.

A new benefit emerged at year 2 in the form of an effect on low-density-lipoprotein cholesterol (P < .002, for MI or LI vs CsA). All groups had comparable rates of malignancies and serious infections. The 3 groups had similar overall safety profiles.

The second study, based on the BENEFIT-EXT (extended criteria) trial, looked at prespecified outcomes in the intent-to-treat population after 2 years. One-year results had shown that extended-criteria donor kidney transplant patients had better renal function when treated with belatacept-based regimens than with CsA-based regimens, and comparable patient/graft survival.

As in the BENEFIT trial, patients were randomized to receive MI belatacept (116 patients completed treatment to year 2); LI belatacept (119 patients completed treatment to year 2); or CsA (112 patients completed treatment to year 2). Overall, 347 of 543 patients completed 2 years of treatment. All patients were treated with basiliximab induction, MMF, and corticosteroids.

All 3 groups had similar patient/graft survival rates at 2 years (83% for MI, 84% for LI, and 83% for CsA).

Improved renal function seen at year 1 remained at year 2, as assessed by GFR (52 mL/min for MI, 50 mL/min for LI, and 45 mL/min for CsA; P = .028 for MI vs CsA; P = .108 for LI vs CsA) and by calculated GFR (8 to 10 mL/min higher with MI and LI than with CsA).

At year 2, patients receiving belatacept continued to benefit from the improved cardiovascular and metabolic risk profiles that were observed at year 1.

Rates of malignancies and serious infections were comparable in all groups. There were 2 cases of PTLD between year 1 and year 2 (1 each with MI and LI); to July 2009 in BENEFIT-EXT, there were 2 cases with MI, 3 with LI, and 0 with CsA; and there were also 3 additional episodes of acute rejection (1 with LI and 2 with CsA).

The researchers concluded that there was no efficacy gained by using the MI regiment instead of the LI regimen.

"A belatacept-based regimen maintained better renal function, a better cardiovascular/metabolic risk profile, and similar patient/graft survival vs CsA at 2 years," the researchers write in their abstract.

"It's revolutionary for the field, because since 1982 we've been working with calcineurin inhibitors. The hope is that there will be no kidney toxicity, reduced cardiovascular events, and an improved metabolic profile for the patients," Antoine Durrbach, MD, PhD, professor of nephrology and transplantation at Bicêtre Hospital in Paris, France, who presented the second study, told Medscape Transplantation.

"It's a promising potential therapy, but the big warning is increased risk of PTLD. And the cases weren't even normal — there was a higher rate of [central nervous system involvement]," session moderator Alden Doyle, MD, MPH, medical director of kidney and pancreas transplantation at Drexel University College of Medicine in Philadelphia, Pennsylvania, told Medscape Transplantation after the belatacept presentations.

Dr. Doyle's interested was piqued by 1 aspect of the study that didn't receive as much emphasis. The study indicated that "there may be less rejection from the humoral side and perhaps less late humoral rejection. There has been increased attention paid to humoral rejection and long-term outcome because there are lots of ways to prevent acute rejection," he noted.

The study was funded by Bristol-Meyers Squibb, the maker of belatacept. Dr. Durrbach and Dr. Doyle have disclosed no relevant financial relationships.

American Transplant Congress (ATC) 2010: Abstracts 142 and 143. Presented May 2, 2010.