Belatacept Conversion in an HIV‐Positive Kidney Transplant Recipient With Prolonged Delayed Graft Function

We report an HIV‐positive renal transplant recipient with delayed graft function who was converted from tacrolimus to belatacept in an attempt to improve renal function. The patient had kidney biopsies at 4 and 8 weeks posttransplant that revealed acute tubular necrosis and mild fibrosis. After 14 weeks of delayed function, belatacept was initiated and tacrolimus was weaned off. Shortly after discontinuing tacrolimus, renal function began to improve. The patient was able to discontinue dialysis 21 weeks posttransplant. HIV viral load was undetectable at last follow‐up. To our knowledge, this is the first report of belatacept use in a patient with HIV.     

ASP2409, A Next‐Generation CTLA4‐Ig,Versus Belatacept in Renal Allograft Survival in Cynomolgus Monkeys

Belatacept is the first costimulatory blockade agent approved for maintenance immunosuppression in kidney transplant recipients. Clinical results have indicated that belatacept is associated with superior renal function and improved metabolic profile; however, higher incidence of acute rejection and posttransplant lymphoproliferative disorder are the shortcomings of this agent. In this study, ASP2409, a new cytotoxic T‐lymphocyte associated protein 4‐immunoglobulin possessing 14‐fold higher in vitro CD86 binding affinity than belatacept, was tested for renal allograft survival in cynomolgus monkeys. ASP2409 monotherapy dose‐dependently prolonged renal allograft survival. Low‐dose ASP2409 in combination with a subtherapeutic dose of tacrolimus showed much longer median survival time than monotherapy. Similar allograft survival results were observed in regimens based on high‐dose ASP2409, belatacept, and therapeutic‐dose tacrolimus. The results of renal allograft histopathology with high‐dose ASP2409‐based regimens were not inferior to the belatacept‐based regimen. Moreover, higher frequencies of FoxP3‐positive regulatory T cells in renal allografts were observed in ASP2409‐ and belatacept‐based regimens compared with tacrolimus‐based regimens. No serious side effects related to ASP2409 administration were found during the study. These data suggest that ASP2409 is a promising candidate for calcineurin inhibitor‐sparing or ‐avoidance regimens.     

Donor evaluation in the era of HIV‐positive organ transplantation: The importance of the infectious diseases specialist

A 61‐year‐old female with well‐controlled human immunodeficiency virus (HIV) and end‐stage renal disease was on the kidney transplant waitlist awaiting an organ offer, including from HIV‐positive donors through the HIV Organ Policy Equity (HOPE) Act. We present three different scenarios where HIV‐positive donor offers were evaluated for this one recipient, discuss the donor evaluation process, explain where the infectious diseases provider fits in this scheme, and describe the challenges encountered by organ procurement organizations. This is the first case under the HOPE Act at our center where discovery of an HIV‐specific issue led to a turndown of an organ offer.     

Long‐Term Outcomes in Belatacept‐ Versus Cyclosporine‐Treated Recipients of Extended Criteria Donor Kidneys: Final Results From BENEFIT‐EXT,a Phase III Randomized Study

In the Belatacept Evaluation of Nephroprotection and Efficacy as First‐Line Immunosuppression Trial–Extended Criteria Donors (BENEFIT‐EXT), extended criteria donor kidney recipients were randomized to receive belatacept‐based (more intense [MI] or less intense [LI]) or cyclosporine‐based immunosuppression. In prior analyses, belatacept was associated with significantly better renal function compared with cyclosporine. In this prospective analysis of the intent‐to‐treat population, efficacy and safety were compared across regimens at 7 years after transplant. Overall, 128 of 184 belatacept MI–treated, 138 of 175 belatacept LI–treated and 108 of 184 cyclosporine‐treated patients contributed data to these analyses. Hazard ratios (HRs) comparing time to death or graft loss were 0.915 (95% confidence interval [CI] 0.625–1.339; p = 0.65) for belatacept MI versus cyclosporine and 0.927 (95% CI 0.634–1.356; p = 0.70) for belatacept LI versus cyclosporine. Mean estimated GFR (eGFR) plus or minus standard error at 7 years was 53.9 ± 1.9, 54.2 ± 1.9, and 35.3 ± 2.0 mL/min per 1.73 m² for belatacept MI, belatacept LI and cyclosporine, respectively (p < 0.001 for overall treatment effect). HRs comparing freedom from death, graft loss or eGFR <20 mL/min per 1.73 m² were 0.754 (95% CI 0.536–1.061; p = 0.10) for belatacept MI versus cyclosporine and 0.706 (95% CI 0.499–0.998; p = 0.05) for belatacept LI versus cyclosporine. Acute rejection rates and safety profiles of belatacept‐ and cyclosporine‐based treatment were similar. De novo donor‐specific antibody incidence was lower for belatacept (p ≤ 0.0001). Relative to cyclosporine, belatacept was associated with similar death and graft loss and improved renal function at 7 years after transplant and had a safety profile consistent with previous reports.     

Belatacept Combined With Transient Calcineurin Inhibitor Therapy Prevents Rejection and Promotes Improved Long‐Term Renal Allograft Function

Belatacept, a T cell costimulation blocker, demonstrated superior renal function, lower cardiovascular risk, and improved graft and patient survival in renal transplant recipients. Despite the potential benefits, adoption of belatacept has been limited in part due to concerns regarding higher rates and grades of acute rejection in clinical trials. Since July 2011, we have utilized belatacept‐based immunosuppression regimens in clinical practice. In this retrospective analysis of 745 patients undergoing renal transplantation at our center, we compared patients treated with belatacept (n = 535) with a historical cohort receiving a tacrolimus‐based protocol (n = 205). Patient and graft survival were equivalent for all groups. An increased rate of acute rejection was observed in an initial cohort treated with a protocol similar to the low‐intensity regimen from the BENEFIT trial versus the historical tacrolimus group (50.5% vs. 20.5%). The addition of a transient course of tacrolimus reduced rejection rates to acceptable levels (16%). Treatment with belatacept was associated with superior estimated GFR (belatacept 63.8 mL/min vs. tacrolimus 46.2 mL/min at 4 years, p < 0.0001). There were no differences in serious infections including rates of cytomegalovirus or BK viremia. We describe the development of a costimulatory blockade‐based strategy that ultimately allows renal transplant recipients to achieve calcineurin inhibitor–free immunosuppression.     

Combination Drug Products for HIV—A Word of Caution for the Transplant Clinician

Modern‐day treatment regimens for human immunodeficiency virus (HIV) are not only highly effective, but are now more often available as convenient fixed‐dose combination products. Furthermore, as medication adherence is of utmost importance in this setting, national guidelines endorse the use of such products. Transplant providers of HIV‐infected patients will undoubtedly encounter these products, some of which contain medications known to drastically alter the metabolism of certain immunosuppressants. Herein, we describe an instance of drug interaction–induced calcineurin inhibitor (CNI) nephrotoxicity in a renal transplant recipient being started on a cobicistat‐containing combination product for HIV. CNI toxicity, in turn, was resolved with the aid of phenytoin as an inducer of drug metabolism. This case underscores the importance of familiarity with newer combination products on the market and constant communication with HIV‐positive transplant recipients and their providers.     

Ten‐year outcomes in a randomized phase II study of kidney transplant recipients administered belatacept 4‐weekly or 8‐weekly

In the phase II IM103‐100 study, kidney transplant recipients were first randomized to belatacept more‐intensive‐based (n = 74), belatacept less‐intensive‐based (n = 71), or cyclosporine‐based (n = 73) immunosuppression. At 3‐6 months posttransplant, belatacept‐treated patients were re‐randomized to receive belatacept every 4 weeks (4‐weekly, n = 62) or every 8 weeks (8‐weekly, n = 60). Patients initially randomized to cyclosporine continued to receive cyclosporine‐based immunosuppression. Cumulative rates of biopsy‐proven acute rejection (BPAR) from first randomization to year 10 were 22.8%, 37.0%, and 25.8% for belatacept more‐intensive, belatacept less‐intensive, and cyclosporine, respectively (belatacept more‐intensive vs cyclosporine: hazard ratio [HR] = 0.95; 95% confidence interval [CI] 0.47‐1.92; P = .89; belatacept less‐intensive vs cyclosporine: HR = 1.61; 95% CI 0.85‐3.05; P = .15). Cumulative BPAR rates from second randomization to year 10 for belatacept 4‐weekly, belatacept 8‐weekly, and cyclosporine were 11.1%, 21.9%, and 13.9%, respectively (belatacept 4‐weekly vs cyclosporine: HR = 1.06, 95% CI 0.35‐3.17, P = .92; belatacept 8‐weekly vs cyclosporine: HR = 2.00, 95% CI 0.75‐5.35, P = .17). Renal function trends were estimated using a repeated‐measures model. Estimated mean GFR values at year 10 for belatacept 4‐weekly, belatacept 8‐weekly, and cyclosporine were 67.0, 68.7, and 42.7 mL/min per 1.73 m², respectively (P<.001 for overall treatment effect). Although not statistically significant, rates of BPAR were 2‐fold higher in patients administered belatacept every 8 weeks vs every 4 weeks.     

Long‐term follow‐up of beta cell replacement therapy in 10 HIV‐infected patients with renal failure secondary to type 1 diabetes mellitus

The approach to transplantation in human immunodeficiency virus (HIV)‐positive patients has been conservative due to fear of exacerbating an immunocompromised condition. As a result, HIV‐positive patients with diabetes were initially excluded from beta cell replacement therapy. Early reports of pancreas transplant in patients with HIV described high rates of early graft loss with limited follow‐up. We report long‐term follow‐up of islet or pancreas transplantation in HIV‐positive type 1 diabetic patients who received a kidney transplant concurrently or had previously undergone kidney transplantation. Although 4 patients developed polyoma viremia, highly active antiretroviral therapy and adequate infectious prophylaxis were successful in providing protection until CD4+ counts recovered. Coordination with HIV providers is critical to reduce the risk of rejection by minimizing drug‐drug interactions. Also, protocols for prophylaxis of opportunistic infections and strategies for monitoring and treating BK viremia are important given the degree of immunosuppression required. This series demonstrates that type 1 diabetic patients with well‐controlled HIV and renal failure can be appropriate candidates for beta cell replacement, with a low rate of infectious complications, early graft loss, and rejection, so excellent long‐term graft survival is possible. Additionally, patients with HIV and cardiovascular contraindications can undergo islet infusion.     

Effect of an Early Switch to Belatacept Among Calcineurin Inhibitor–Intolerant Graft Recipients of Kidneys From Extended‐Criteria Donors

Transplant recipients receiving a kidney from an extended‐criteria donor (ECD) are exposed to calcineurin inhibitor (CNI) nephrotoxicity, as demonstrated by severe delayed graft function and/or a low GFR. Belatacept is a nonnephrotoxic drug that is indicated as an alternative to CNIs. We reported 25 cases of conversion from a CNI to belatacept due to CNI intolerance within the first 6 mo after transplantation. The mean age of the recipients was 59 years, and 24 of 25 patients received ECD kidneys. At the date of the medication switch, 12 of 25 patients displayed a calculated GFR (cGFR) <15 mL/min, six patients remained on dialysis, and the biopsies showed evidence of acute tubular damage associated with severe vascular or tubulointerstitial chronic lesions. Three patients did not recover renal function, and three patients died during the follow‐up period. Among the remaining patients, renal function improved: The cGFR was 18.28 ± 12.3 mL/min before the medication switch compared with 34.9 ± 14.5 mL/min at 1 year after conversion to belatacept (p = 0.002). Tolerance of and compliance with belatacept were good, and only one patient experienced acute rejection. Belatacept is an effective therapy that preserves renal function in kidney transplant patients who are intolerant of CNIs.     

Posttransplant reduction in preexisting donor‐specific antibody levels after belatacept‐ versus cyclosporine‐based immunosuppression: Post hoc analyses of BENEFIT and BENEFIT‐EXT

BENEFIT and BENEFIT‐EXT were phase III studies of cytotoxic T‐cell crossmatch–negative kidney transplant recipients randomized to belatacept more intense (MI)‐based, belatacept less intense (LI)‐based, or cyclosporine‐based immunosuppression. Following study completion, presence/absence of HLA‐specific antibodies was determined centrally via solid‐phase flow cytometry screening. Stored sera from anti‐HLA–positive patients were further tested with a single‐antigen bead assay to determine antibody specificities, presence/absence of donor‐specific antibodies (DSAs), and mean fluorescent intensity (MFI) of any DSAs present. The effect of belatacept‐based and cyclosporine‐based immunosuppression on MFI was explored post hoc in patients with preexisting DSAs enrolled to BENEFIT and BENEFIT‐EXT. In BENEFIT, preexisting DSAs were detected in 4.6%, 4.9%, and 6.3% of belatacept MI‐treated, belatacept LI‐treated, and cyclosporine‐treated patients, respectively. The corresponding values in BENEFIT‐EXT were 6.0%, 5.7%, and 9.2%. In both studies, most preexisting DSAs were of class I specificity. Over the first 24 months posttransplant, a greater proportion of preexisting DSAs in belatacept‐treated versus cyclosporine‐treated patients exhibited decreases or no change in MFI. MFI decline was more apparent with belatacept MI‐based versus belatacept LI‐based immunosuppression in both studies and more pronounced in BENEFIT‐EXT versus BENEFIT. Although derived post hoc, these data suggest that belatacept‐based immunosuppression decreases preexisting DSAs more effectively than cyclosporine‐based immunosuppression.     

Comparison of Utilization and Clinical Outcomes for Belatacept‐ and Tacrolimus‐Based Immunosuppression in Renal Transplant Recipients

The performance of belatacept in a real clinical setting has not been reported. A retrospective cohort study was conducted using registry data comparing 1‐year clinical outcomes between belatacept‐ and tacrolimus‐treated adult kidney transplant recipients (KTRs) from January 6, 2011, through January 12, 2014. Of 50 244 total patients, 417 received belatacept plus tacrolimus, 458 received belatacept alone, and 49 369 received tacrolimus alone at discharge. In the overall study cohort, belatacept alone was associated with a higher risk of 1‐year acute rejection, with the highest rates associated with non–lymphocyte‐depleting induction (adjusted hazard ratio 2.65, 95% confidence interval 1.90–3.70, p < 0.0001). There was no significant difference in rejection rates between belatacept plus tacrolimus and tacrolimus alone. In KTRs who met inclusion criteria for the Belatacept Evaluation of Nephroprotection and Efficacy as First‐line Immunosuppression Trial–Extended Criteria Donors (BENEFIT‐EXT), 1‐year kidney function was higher with belatacept plus tacrolimus and belatacept alone versus tacrolimus alone (mean estimated GFR 65.6, 60.4 and 54.3 mL/min per 1.73 m², respectively; p < 0.001). The incidence of new‐onset diabetes after transplantation was significantly lower with belatacept plus tacrolimus and belatacept alone versus tacrolimus alone (1.7%, 2.2%, and 3.8%, respectively; p = 0.01). Despite improved graft function and metabolic complications with belatacept alone, it may be advisable to add short‐term tacrolimus in the first year after transplant and to consider lymphocyte‐depleting induction in patients with high rejection risk, as the risk–benefit ratio allows.     

The impact of belatacept on third‐party HLA alloantibodies in highly sensitized kidney transplant recipients

Recent evidence suggests that belatacept reduces the durability of preexisting antibodies to class I and class II human leukocyte antigens (HLAs). In this case series of 163 highly sensitized kidney transplant candidates whose calculated panel‐reactive antibody (cPRA) activity was ≥98% to 100%, the impact of belatacept on preexisting HLA antibodies was assessed. Of the 163 candidates, 72 underwent transplantation between December 4, 2014 and April 15, 2017; 60 of these transplanted patients remained on belatacept consecutively for at least 6 months. We observed a decrease in the breadth and/or strength of HLA class I antibodies as assessed by FlowPRA in belatacept‐treated patients compared to controls who did not receive belatacept. Specifically, significant HLA antibody reduction was evident for class I (P < .0009). Posttransplant belatacept‐treated patients also had a clinically significant reduction in their cPRA compared to controls (P < .01). Collectively, these findings suggest belatacept can reduce HLA class I antibodies in a significant proportion of highly sensitized recipients and could be an option to improve pretransplant compatibility with organ donors.     

Phase I study of single‐dose pharmacokinetics and pharmacodynamics of belatacept in adolescent kidney transplant recipients

Belatacept is an intravenously infused selective T cell costimulation blocker approved for preventing organ rejection in renal transplant recipients aged ≥18 years. This phase I trial examined the pharmacokinetics and pharmacodynamics (percentage CD86 receptor occupancy [%CD86RO]) of a single dose of belatacept (7.5 mg/kg) administered to kidney transplant recipients aged 12‐17 years receiving a stable calcineurin inhibitor–based immunosuppressive regimen. Nine adolescents (mean age 15.1 years) who were seropositive for Epstein‐Barr virus were enrolled; all completed the 6‐month study. Pharmacokinetics suggested relatively low variability of exposure (coefficients of variation for maximum observed serum concentration [C_max] and area under the serum concentration‐time curve from time zero extrapolated to infinity [AUC_0‐INF] were 20% and 25%, respectively). Mean half‐life (T_1/2) occurred 7.2 days postinfusion. Belatacept total body clearance was 0.48 mL/h/kg, and volume of distribution at steady‐state (V_ss) was low at 0.09 L/kg. Compared with historical data from healthy adult volunteers administered a single dose of belatacept 10 mg/kg and adult kidney transplant recipients administered multiple doses of belatacept 5 mg/kg, pharmacokinetic values for adolescents were similar, indicating consistency across adolescent and adult populations. Mean %CD86RO increased with increasing belatacept concentration, indicating a direct relationship between pharmacokinetics and pharmacodynamics. Four patients reported 7 serious adverse events; none was considered related to belatacept. These data will inform belatacept dose selection in future studies of adolescent kidney transplant recipients.     

Comparison of de novo IgM and IgG anti‐HLA DSAs between belatacept‐ and calcineurin‐treated patients: An analysis of the BENEFIT and BENEFIT‐EXT trial cohorts

Preventing conversion of donor‐specific anti‐HLA antibodies (DSAs) from an IgM‐to‐IgG could a way to prevent chronic rejection. We evaluated whether belatacept‐treated patients (belatacept less‐intensive [LI] or more‐intensive [MI] regimens) have a lower rate of conversion than do cyclosporine A (CsA)–treated patients. We included 330 HLA‐mismatched patients from 2 phase 3 trials with either (a) complete donor/recipient HLA‐A, ‐B, ‐DR, and ‐DQ loci typing or (b) incomplete HLA typing with IgG DSAs detected pretransplant or posttransplant. IgM and IgG DSAs were tested with single antigen beads at 0, 6, 12, 24, and 36 months posttransplant. The overall (preexisting or de novo) rates of IgM‐ and IgG‐positive DSAs were 29% and 34%, respectively. The pretransplant IgM and IgG DSA‐positive frequencies were similar between treatment groups. The IgG‐positive dnDSA rate was significantly higher in the CsA‐treated group (34%) compared with the belatacept‐LI (8%) and belatacept‐MI (11%) (P < .001) groups. In IgM‐positive dnDSA patients, the IgG‐positive dnDSA rate of conversion was 2.8 times higher in the CsA group than in the combined belatacept groups (P = .006). However, the observed association between belatacept treatment and more limited conversion of IgM‐to‐IgG dnDSAs was based on a limited number of patients and requires further validation.     

De novo belatacept in clinical vascularized composite allotransplantation

Most immunosuppressive regimens used in clinical vascularized composite allotransplantation (VCA) have been calcineurin inhibitor (CNI)‐based. As such, most recipients have experienced CNI‐related side effects. Costimulation blockade, specifically CD28/B7 inhibition with belatacept, has emerged as a clinical replacement for CNI‐based immunosuppression in kidney transplantation. We have previously shown that belatacept can be used as a centerpiece immunosuppressant for VCA in nonhuman primates, and subsequently reported successful conversion from a CNI‐based regimen to a belatacept‐based regimen after clinical hand transplantation. We now report on the case of a hand transplant recipient, whom we have successfully treated with a de novo belatacept‐based regimen, transitioned to a CNI–free regimen. This case demonstrates that belatacept can provide sufficient prophylaxis from rejection without chronic CNI‐associated side effects, a particularly important goal in nonlifesaving solid organ transplants such as VCA.     

Abatacept as rescue immunosuppression after calcineurin inhibitor treatment failure in renal transplantation

A majority of kidney transplant recipients receive calcineurin inhibitor‐based immunosuppression. However, some do not tolerate calcineurin inhibitors and require other immunosuppressive strategies. Until recently, alternative approaches have been associated with inferior outcomes, but recent methods have effectively utilized belatacept in calcineurin inhibitor‐intolerant patients. Though promising, belatacept uptake has been limited by higher acute rejection rates, unavailability due to production shortages, and logistical challenges as a result of intravenous infusion requirements. Interestingly, its predecessor abatacept is clinically available in subcutaneous formulation to treat autoimmune disorders but has not been used in clinical transplantation. Here we report on a series of 9 calcineurin inhibitor‐intolerant transplant recipients converted to abatacept early after transplant as rescue immunosuppression during periods of belatacept unavailability. Retrospective review revealed successful allograft salvage and 100% patient and graft survival (median 115 months) after conversion to abatacept. Patients received abatacept for a median duration of 82 months with stable, long‐term renal allograft function, a single cellular rejection episode, and no clinically apparent protective immunity concerns. Hence our findings suggest that future clinical studies utilizing abatacept either de novo or as conversion therapy in transplant recipients should be considered.     

Association Between Duration of Human Immunodeficiency Virus (HIV)–1 Viral Suppression Prior to Renal Transplantation and Acute Cellular Rejection

Renal transplant has become an important option for human immunodeficiency virus (HIV)–infected patients with end‐stage renal disease; however, these patients experience a high rate of acute cellular rejection (ACR). Guidelines do not currently exist for the optimal duration of viral suppression prior to transplantation. In a retrospective cohort analysis of 47 HIV‐infected renal transplant recipients, we compared the rate of ACR between patients based on the length of time of viral suppression prior to transplantation. Of the patients who achieved viral suppression for >6 months but less than 2 years prior to transplantation (n = 15), 60% experienced ACR compared to 41% of patients suppressed at least 2 years or more (n = 32) prior to transplant (p = 0.21). Patients suppressed <2 years experienced ACR at 2.48 times the rate of those suppressed 2 years or longer. Induction immunosuppression, HLA mismatch and panel‐reactive antibodies (PRAs) did not significantly differ between the two groups.     

Belatacept during pregnancy in renal transplant recipients: Two case reports

Impaired fertility is common among patients with chronic organ failure, including end‐stage renal disease (ESRD). Women of childbearing age undergoing transplantation may experience rapid return of fertility. Pregnancy posttransplant presents numerous risks for the patient, fetus, and allograft. Maternal risks include hypertension and preeclampsia. Allograft risks include acute rejection and failure of the organ, and fetal risks include miscarriage, birth defects from immunosuppressants, premature delivery, and low birth weight. Belatacept, a selective T cell costimulation blocker, was approved for use in kidney transplant recipients in the United States in 2011. Little is known about the safety of belatacept during pregnancy in humans. We describe 2 cases of successful pregnancy and delivery with the use of belatacept‐based immunosuppression. The Transplant Pregnancy Registry International (TPR) is a voluntary registry for transplant recipients who have had pregnancies or fathered a pregnancy posttransplant. To date, these 2 cases are the only known exposures to belatacept that have been reported to the TPR. 1     

Long‐term survival after kidney transplantation in an HIV‐positive patient

Abstract: Only a decade ago, human immunodeficiency virus (HIV)‐seropositivity was considered an absolute contraindication for organ transplantation. With the currently available experience, it is no longer justified to deny HIV‐positive patients access to transplantation. To the best of our knowledge, we here present the longest surviving HIV‐positive patient after renal transplantation. The follow‐up period after renal transplantation in this HIV‐positive female is now 13 yr and she is in good general condition with excellent renal function. Throughout her post‐transplant follow‐up, we encountered a number of problems that are illustrative of the HIV‐positive patient.     

De novo donor‐specific antibodies in belatacept‐treated vs cyclosporine‐treated kidney‐transplant recipients: Post hoc analyses of the randomized phase III BENEFIT and BENEFIT‐EXT studies

Donor‐specific antibodies (DSAs) are associated with an increased risk of antibody‐mediated rejection and graft failure. In BENEFIT and BENEFIT‐EXT, kidney‐transplant recipients were randomized to receive belatacept more intense (MI)–based, belatacept less intense (LI)–based, or cyclosporine‐based immunosuppression for up to 7 years (84 months). The presence/absence of HLA‐specific antibodies was determined at baseline, at months 6, 12, 24, 36, 48, 60, and 84, and at the time of clinically suspected episodes of acute rejection, using solid‐phase flow‐cytometry screening. Samples from anti‐HLA‐positive patients were further tested with a single‐antigen bead assay to determine antibody specificities, presence/absence of DSAs, and mean fluorescence intensity (MFI) of any DSAs present. In BENEFIT, de novo DSAs developed in 1.4%, 3.5%, and 12.1% of belatacept MI‐treated, belatacept LI‐treated, and cyclosporine‐treated patients, respectively. The corresponding values in BENEFIT‐EXT were 3.8%, 1.1%, and 11.2%. Per Kaplan‐Meier analysis, de novo DSA incidence was significantly lower in belatacept‐treated vs cyclosporine‐treated patients over 7 years in both studies (P < .01). In patients who developed de novo DSAs, belatacept‐based immunosuppression was associated with numerically lower MFI vs cyclosporine‐based immunosuppression. Although derived post hoc, these data suggest that belatacept‐based immunosuppression suppresses de novo DSA development more effectively than cyclosporine‐based immunosuppression.