Approved as Skysona, the therapy has been reported to be related to cases of hematologic malignancies, including life-threatening instances of myelodysplastic syndrome and acute myeloid leukemia.
To report suspected adverse events including hematologic malignancies, contact the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Healthcare providers, clinical investigators, patients, and caregivers who have questions may contact FDA’s Center for Biologics Evaluation and Research (CBER) at ocod@fda.hhs.gov.
The FDA has announced it will be investigating a number of reports it has recieved on bluebird bio's approved autologous hematopoietic stem cell (HSC)-based gene therapy elivaldogene autotemcel (eli-cel; marketed as Skysona), related to incidence of hematologic malignancies. In its announcement, the agency noted that some of these cases have included life-threatening cases of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) in patients with early, active cerebral adrenoleukodystrophy (CALD).1
Notably, the agency mentioned that reports were received from clinical trials, with these cases diagnosed between 14 to 92 months after treatment with elivaldogene autotemcel.
"FDA is investigating the known risk of hematologic malignancies with serious outcomes, including those such as hospitalization, the requirement for allogeneic hematopoietic stem cell transplantation, and death, and is evaluating the need for further regulatory action," the agency stated. As hematologic malignancies pose a serious risk to patients, the agency is urging health care providers to carefully consider alternative treatments at this time—including allogeneic hematopoietic stem cell transplant (HCST) for patients who have a suitable, willing, and available human leukocyte antigen-matched donor—prior to deciding to move ahead with elivaldogene autotemcel.
The therapy's prescribing information on its US-base label does include information on the risk of developing these malignancies in a Boxed Warning, and under its Warnings and Precautions and Clinical Trials Experience section.2 The FDA noted that patients, including those who are participants in clinical trials, who are receiving the gene therapy should be monitored for these malignancies for life.
"Therefore, patients should be closely monitored with complete blood counts at least every 3 months and through assessments for evidence of clonal expansion or predominance at least twice in the first year after Skysona administration and annually thereafter, and bone marrow evaluations should be considered as clinically indicated," the agency noted.1 If hematologic malignancy is detected, providers should report the event to the manufacturer, at which time instructions will be provided on how and when to properly collect of samples for further testing.
This announcement comes after
In total 1 of 32 patients treated in ALD-102 and 6 of 35 patients treated in ALD-104 were diagnosed with hematologic malignancies following treatment. A single patient developed MDS with unilineage dysplasia at 14 months posttreatment and another was diagnosed with the same at 26 months posttreatment, while another 3 patients were diagnosed with MDS with excess blasts at 28 months, 42 months, and 92 months posttreatment, respectively. A fifth patient was diagnosed with MDS at 36 months posttreatment, and another 1 patient developed AML at 57 months posttreatment.
Among those 7 individuals, 6 remained alive as of the data's publication, with 1 patient having died 49 months after treatment with eli-cel. This patient had received allogeneic HSCT for treatment of their MDS, and their death 20 months after receiving HSCT was attributed to presumed graft-versus-host disease.
