On December 15, 2021, abatacept, a selective T-cell costimulation modulator, was approved for prophylaxis of acute graft-vs-host disease in combination with a calcineurin inhibitor (eg, cyclosporine, tacrolimus) and methotrexate in adults and pediatric patients aged ≥ 2 years undergoing hematopoietic stem cell transplantation (HSCT) from a matched or 1 allele-mismatched unrelated donor.1
Supporting Efficacy Data
Approval was based on findings in the randomized, double-blind GVHD-1 study (ClinicalTrials.gov identifier NCT01743131) and data from a real-world registry-based study (GVHD-2).
In the GVHD-1 trial, patients with hematologic malignancies undergoing an 8 of 8 human leukocyte antigen (HLA)-matched HSCT received abatacept (n = 73) or placebo (n = 69) in combination with a calcineurin inhibitor and methotrexate. At posttransplantation day 180, grade III to IV acute graft-vs-host disease–free survival was 87% vs 75% (hazard ratio [HR] = 0.55, 95% confidence interval [CI] = 0.26–1.18), overall survival was 97% vs 84% (HR = 0.33, 95% CI = 0.12–0.93), and grade II to IV graft-vs-host disease–free survival was 50% vs 32% (HR = 0.54, 95% CI = 0.35–0.83). In the GVHD-2, study overall survival at day 180 after a 7 of 8 HLA-matched HSCT was 98% among 54 patients receiving abatacept plus a calcineurin inhibitor and methotrexate vs 75% among 162 patients receiving a calcineurin inhibitor and methotrexate without abatacept.
How It Is Used
Abatacept dosing for patients aged aged 6 and older is 10 mg/kg (maximum dose of 1,000 mg) via intravenous (IV) infusion on the day before transplantation (day –1) and on posttransplantation days 5, 14, and 28. Patients between the ages of 2 and 6 receive 15 mg/kg via IV infusion on the day before transplantation (day –1) and 12 mg/kg on days 5, 14, and 28.
OF NOTE
Abatacept has warnings/precautions for concomitant use with a tumor necrosis factor antagonist, hypersensitivity and anaphylaxis, serious infections, screening for latent tuberculosis, screening for viral hepatitis, live vaccines, use in patients with chronic obstructive pulmonary disease, and CMV and EBV reactivation.
Prophylaxis for Epstein-Barr virus (EBV) reactivation should be given and continued for 6 months following HSCT. Prophylaxis should be considered for cytomegalovirus (CMV) infection or reactivation during treatment and for 6 months following HSCT.
Safety Profile
Safety data are from 116 patients who received abatacept in the GVHD-1 trial, including 43 patients from a single-arm HLA 7 of 8 matched cohort and 73 from the HLA 8 of 8 matched randomized comparison. The most common adverse events of any grade with abatacept (≥ 10%) were anemia, hypertension, CMV reactivation or infection, pyrexia, pneumonia, epistaxis, decreased CD4 lymphocytes, hypermagnesemia, and acute kidney injury. In the comparative cohort, the most common grade 3 or 4 adverse events were anemia (69% vs 57% in the calcineurin inhibitor/methotrexate group), hypertension (43% vs 38%), and CMV reactivation or infection (32% vs 22%).
Overall, the most common serious adverse events were pyrexia (20%), pneumonia (8%), and acute kidney injury (7%). Treatment was discontinued due to adverse events in two patients (1.7%).
Abatacept has warnings/precautions for concomitant use with a tumor necrosis factor antagonist, hypersensitivity and anaphylaxis, serious infections, screening for latent tuberculosis, screening for viral hepatitis, live vaccines, use in patients with chronic obstructive pulmonary disease, and CMV and EBV reactivation.
REFERENCE
1. Orencia (abatacept) for injection, for intravenous use, Bristol Myers Squibb Company, December 2021. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/125118s240lbl.pdf. Accessed December 21, 2021.
