FDA Investigating Risk of Hematologic Malignancy Following CALD Gene Therapy

December 05, 2024

The Food and Drug Administration is investigating additional reports of hematologic malignancies, including life-threatening cases of myelodysplastic syndrome and acute myeloid leukemia, in patients treated with elivaldogene autotemcel (eli-cel), marketed as Skysona by Bluebird Bio.

FDA approved eli-cel in 2022 for early, active cerebral adrenoleukodystrophy (CALD) with a boxed warning for hematologic malignancies, which were observed during clinical trials.

Since its approval, FDA has received additional reports of malignancies related to eli-cel, with cases occurring between 14 and 92 months post-treatment. Some cases resulted in hospitalization, the need for allogeneic hematopoietic stem cell transplantation or death.

The FDA advises providers to consider alternative therapies, such as allogeneic hematopoietic stem cell transplant, for patients with a suitable donor before opting for eli-cel. Additionally, patients who do receive eli-cel should receive lifelong monitoring for signs of hematologic malignancy. This includes conducting complete blood counts every three months and annual monitoring for clonal expansion. Clinicians should also consider bone marrow evaluations as needed and report any malignancy to the manufacturer for further testing.

Eli-cel’s approval included a 15-year postmarketing safety study to assess the long-term risks of secondary malignancies. Clinicians should report suspected adverse events to the FDA via MedWatch program.