THURSDAY, Oct. 10, 2024 (HealthDay News) -- Hematologic cancer develops in some patients receiving lentiviral elivaldogene autotemcel (eli-cel) gene therapy for cerebral adrenoleukodystrophy, according to a study published in the Oct. 10 issue of the New England Journal of Medicine.
Christine N. Duncan, M.D., from Harvard Medical School in Boston, and colleagues analyzed peripheral-blood and bone marrow samples from patients with cerebral adrenoleukodystrophy who received eli-cel therapy in two completed phase 2 to 3 studies (ALD-102 [32 patients] and ALD-104 [35 patients]) and the associated ongoing follow-up study (LTF-304) to examine the risk for oncogenesis with eli-cel.
The researchers found that seven of 67 patients developed hematologic cancer after receipt of eli-cel: Myelodysplastic syndrome (MDS) with unilineage dysplasia developed in two patients at 14 and 26 months; MDS with excess blasts developed in three patients at 28, 42, and 92 months; MDS developed in one patient at 36 months; and acute myeloid leukemia developed in one patient at 57 months. Predominant clones contained lentiviral vector insertions at multiple loci in the six patients with available data. Cytopenias developed in several patients; most had vector insertions in multiple genes within the same clone. Of the seven patients, six also had somatic mutations and one had monosomy 7. Four of the five patients with MDS with excess blasts or MDS with unilineage dysplasia who underwent allogeneic hematopoietic stem cell transplantation (HSCT) remain free of MDS without recurrence of cerebral adrenoleukodystrophy symptoms.
"The risk of oncogenesis with eli-cel must be weighed against the severity and natural history of cerebral adrenoleukodystrophy as well as the availability of other treatments and their risks, including allogeneic HSCT," the authors write.
The study was funded by Bluebird Bio, the manufacturer of eli-cel.
Abstract/Full Text (subscription or payment may be required)
Editorial (subscription or payment may be required)
