BMS Updates Safety Label of Reblozyl

BMS warns about the risk of extramedullary hematopoiesis, a rare complication in which the production of blood cells occurs outside of the bone marrow.

Bristol Myers Squibb has added a new subsection in the warnings section the label of Reblozyl (luspatercept-aamt) to warn about the risk of extramedullary hematopoietic masses in adult patients with transfusion dependent beta thalassemia.

Reblozyl, a first-in-class therapeutic option, is currently approved in the United States, European Union and Canada to address transfusion-dependent anemia-associated beta thalassemia and lower-risk myelodysplastic syndromes. Beta thalassemia is an inherited blood disorder caused by a genetic defect in hemoglobin. It is being developed and commercialized through a collaboration between Bristol Myers Squibb and Merck, following Merck’s acquisition of Acceleron Pharma in November 2021.

Extramedullary hematopoiesis (EMH) is a complication that occurs in patients with beta thalassemia and is more common in patients with non-transfusion dependent (NTD) beta thalassemia than transfusion-dependent (TD) disease. EMH involves the production of blood cells outside of the bone marrow and can occur in various organs. It is rarely reported in patients with myelodysplastic syndromes.

In adult patients with transfusion-dependent beta thalassemia, extramedullary hematopoiesis masses were observed in 3.2% of Reblozyl-treated patients, with spinal cord compression symptoms due to EMH masses occurring in 1.9% of patients. These were the findings from the BELIEVE trial and long-term follow up studies (ACE-536-LTFU-001).

In the BEYOND study of adult patients with non-transfusion dependent beta thalassemia, a higher incidence of extramedullary hematopoiesis was observed in 6.3% of Reblozyl-treated patients vs. 2% of placebo-treated patients in the double-blind phase of the study, with spinal cord compression due to EMH masses occurring in one patient with a prior history of EMH.

“Based on these data, we worked closely with the FDA to determine the appropriate updates to the Reblozyl label,” a spokesperson for Bristol Myers Squibb told Formulary Watch. “These clinical trial data have not been separately published beyond what’s included in this update. At Bristol Myers Squibb, patient safety is our highest priority, and we are committed to ensuring the safety of our therapies is well-defined.”

This addition to the label follows the company’s move to withdraw the supplemental biologics license application (sBLA) for Reblozyl for the non-transfusion dependent beta thalassemia indication. BMS said in a press release that it could not appropriately address the FDA’s questions about the benefit-risk profile of Reblozyl in this patient population based on the current data from the BEYOND trial.

Related: BMS Withdraws sBLA for Reblozyl for Rare Blood Disorder

Data from the phase 2 BEYOND trial were presented at the European Hematology Association Virtual Congress in June 2021.

The newly added subsection reads:

“In adult patients with transfusion dependent beta thalassemia, EMH masses were observed in 3.2% of Reblozyl-treated patients, with spinal cord compression symptoms due to EMH masses occurring in 1.9% of patients (BELIEVE and Reblozyl long-term follow-up study).

“In a study of adult patients with non-transfusion dependent beta thalassemia, a higher incidence of EMH masses was observed in 6.3% of Reblozyl-treated patients vs. 2% of placebo-treated patients in the double-blind phase of the study, with spinal cord compression due to EMH masses occurring in 1 patient with a prior history of EMH. Reblozyl is not indicated for use in patients with non-transfusion dependent beta-thalassemia.

“Possible risk factors for the development of EMH masses in patients with beta thalassemia include history of EMH masses, splenectomy, splenomegaly, hepatomegaly, or low baseline hemoglobin (<8.5 g/dL). Signs and symptoms may vary depending on the anatomical location. Monitor patients with beta thalassemia at initiation and during treatment for symptoms and signs or complications resulting from the EMH masses and treat according to clinical guidelines. Discontinue treatment with Reblozyl in case of serious complications due to EMH masses. Avoid use of Reblozyl in patients requiring treatment to control the growth of EMH masses.”