Use of belatacept as alternative graft vs host disease prophylaxis in pediatric allogeneic hematopoietic stem cell transplantation.

Immunosuppressive prophylaxis is usually given to decrease the development of acute graft versus host disease (GvHD) after allogeneic hematopoietic stem cell transplantation (HSCT). Belatacept is a Cytotoxic T-lymphocyte-associated protein 4, blocking agent, an immunosuppressive agent used for organ rejection prevention in adult renal transplant recipients. We describe two children in whom belatacept was successfully used for GvHD prophylaxis. Case 1 was noncompliant with prior immunosuppressive therapy for aplastic anemia, and Case 2 developed severe thrombotic microangiopathy (TMA) precluding the use of calcineurin inhibitors (CNI) or mTOR inhibitors. Belatacept was found to be a safe alternative in preventing GvHD in 2 patients in whom traditional prophylactic therapies were not possible to use.

Wright M ，Rangarajan H ，Abu-Arja R ，Auletta JJ ，Lee D ，Polishchuk V ，Pai V ，Taylor K ，Bajwa RPS ... -  《-》

A Difficult Case of Calcineurin Inhibitor Neurotoxicity Post-Haploidentical HCT With a Successful Novel Solution: Cytotoxic T-Lymphocyte-Associated Protein 4-Immunoglobulin Blockade for GVHD Prophylaxis.

Dykes K ，Tzachanis D ，Koura D 《-》

Graft-versus-host Disease Prophylaxis With Abatacept Reduces Severe Acute Graft-versus-host Disease in Allogeneic Hematopoietic Stem Cell Transplant for Beta-thalassemia Major With Busulfan, Fludarabine, and Thiotepa.

We hypothesized that the addition of 4 doses of abatacept to our standard acute graft-versus-host disease (GVHD) prophylaxis would reduce the incidence of day +100 severe acute GVHD in children with transfusion-dependent beta-thalassemia major undergoing a myeloablative allogeneic hematopoietic stem cell transplant (HSCT), without impacting engraftment. Twenty-four children with beta-thalassemia major received abatacept at a dose of 10 mg/kg intravenously on days -1, +5, +14, and +28 after HSCT in addition to calcineurin inhibitors and methylprednisolone. Outcomes were compared to 8 beta-thalassemia patients who received standard acute GVHD prophylaxis. There was no difference in engraftment between the 2 groups. No patient had grades III-IV acute GVHD by day +100 in the abatacept cohort compared with 50% in the standard acute GVHD prophylaxis group (P = 0.001). Viral reactivation occurred in 5 children in the standard acute GVHD cohort and in 20 children in the abatacept cohort (P = 0.2). Thalassemia-free survival after HSCT was 100% in the abatacept cohort compared to 62.5% in the standard cohort at last follow-up (P = 0.007). Adding abatacept to our routine GVHD prophylaxis reduced the incidence of day +100 severe acute GVHD without impacting engraftment or survival.

Khandelwal P ，Yeh RF ，Yu L ，Lane A ，Dandoy CE ，El-Bietar J ，Davies SM ，Grimley MS ... -  《-》

Post-transplantation cyclophosphamide reduces the incidence of acute graft-versus-host disease in patients with acute myeloid leukemia/myelodysplastic syndromes who receive immune checkpoint inhibitors after allogeneic hematopoietic stem cell transplantat

Immune checkpoint inhibitors (ICIs) are being used after allogeneic hematopoietic stem cell transplantation (alloHCT) to reverse immune dysfunction. However, a major concern for the use of ICIs after alloHCT is the increased risk of graft-versus-host disease (GVHD). We analyzed the association between GVHD prophylaxis and frequency of GVHD in patients who had received ICI therapy after alloHCT. A retrospective study was performed in 21 patients with acute myeloid leukemia (n=16) or myelodysplastic syndromes (n=5) who were treated with antiprogrammed cell death protein 1 (16 patients) or anticytotoxic T lymphocyte-associated antigen 4 (5 patients) therapy for disease relapse after alloHCT. Associations between the type of GVHD prophylaxis and incidence of GVHD were analyzed. Four patients (19%) developed acute GVHD. The incidence of acute GVHD was associated only with the type of post-transplantation GVHD prophylaxis; none of the other variables included (stem cell source, donor type, age at alloHCT, conditioning regimen and prior history of GVHD) were associated with the frequency of acute GVHD. Twelve patients received post-transplantation cyclophosphamide (PTCy) for GVHD prophylaxis. Patients who received PTCy had a significantly shorter median time to initiation of ICI therapy after alloHCT compared with patients who did not receive PTCy (median 5.1 months compared with 26.6 months). Despite early ICI therapy initiation, patients who received PTCy had a lower observed cumulative incidence of grades 2-4 acute GVHD compared with patients who did not receive PTCy (16% compared with 22%; p=0.7). After controlling for comorbidities and time from alloHCT to ICI therapy initiation, the analysis showed that PTCy was associated with a 90% reduced risk of acute GVHD (HR 0.1, 95% CI 0.02 to 0.6, p=0.01). ICI therapy for relapsed acute myeloid leukemia/myelodysplastic syndromes after alloHCT may be a safe and feasible option. PTCy appears to decrease the incidence of acute GVHD in this cohort of patients.

Saberian C ，Abdel-Wahab N ，Abudayyeh A ，Rafei H ，Joseph J ，Rondon G ，Whited L ，Gruschkus S ，Fa'ak F ，Daher M ，Knape C ，Safa H ，Shoukier M ，Suarez-Almazor ME ，Marcotulli M ，Ludford K ，Gulbis AM ，Konopleva M ，Ohanian M ，Ravandi F ，Garcia-Manero G ，Oran B ，Popat UR ，Mehta R ，Alousi AM ，Daver N ，Champlin R ，Diab A ，Al-Atrash G ... -  《Journal for ImmunoTherapy of Cancer》

Safety and Efficacy Outcomes 3 Years After Switching to Belatacept From a Calcineurin Inhibitor in Kidney Transplant Recipients: Results From a Phase 2 Randomized Trial.

In a phase 2 study, kidney transplant recipients of low immunologic risk who switched from a calcineurin inhibitor (CNI) to belatacept had improved kidney function at 12 months postconversion versus those continuing CNI therapy, with a low rate of acute rejection and no transplant loss. 36-month follow-up of the intention-to-treat population. CNI-treated adult kidney transplant recipients with stable transplant function (estimated glomerular filtration rate [eGFR], 35-75mL/min/1.73m2). At 6 to 36 months posttransplantation, patients were randomly assigned to switch to belatacept-based immunosuppression (n=84) or continue CNI-based therapy (n=89). Safety was the primary outcome. eGFR, acute rejection, transplant loss, and death were also assessed. Treatment exposure-adjusted incidence rates for safety, repeated-measures modeling for eGFR, Kaplan-Meier analyses for efficacy. Serious adverse events occurred in 33 (39%) belatacept-treated patients and 36 (40%) patients in the CNI group. Treatment exposure-adjusted incidence rates for serious infections (belatacept vs CNI, 10.21 vs 9.31 per 100 person-years) and malignancies (3.01 vs 3.41 per 100 person-years) were similar. More patients in the belatacept versus CNI group had any-grade viral infections (14.60 vs 11.00 per 100 person-years). No posttransplantation lymphoproliferative disorder was reported. Belatacept-treated patients had a significantly greater estimated gain in mean eGFR (1.90 vs 0.07mL/min/1.73m2 per year; P for time-by-treatment interaction effect = 0.01). The probability of acute rejection was not significantly different for belatacept (8.38% vs 3.60%; HR, 2.50 [95% CI, 0.65-9.65; P=0.2). HR for the comparison of belatacept to the CNI group for time to death or transplant loss was 1.00 (95% CI, 0.14-7.07; P=0.9). Exploratory post hoc analysis with a small sample size. Switching patients from a CNI to belatacept may represent a safe approach to immunosuppression and is being further explored in an ongoing phase 3b trial.

Grinyó JM ，Del Carmen Rial M ，Alberu J ，Steinberg SM ，Manfro RC ，Nainan G ，Vincenti F ，Jones-Burton C ，Kamar N ... -  《-》