The use of the gene therapy elivaldogene autotemcel (Skysona), has been approved due to its success in the treatment of patients diagnosed with the neurological disease cerebral adrenoleukodystrophy (CALD).
The list of CALD symptoms includes, but is not limited to:
• vision problems.
• seizures.
• poor coordination
• deafness
• difficulty swallowing and
• inability to speak or respond.
However, the approval is accompanied by a caveat emerging from the two studies warning of the risk of hematologic cancers. A report in Med Page Today documented the death of seven boys after treatment with eli-cel. The boys were among a group of 67 who had CALD. The deaths occurred within 14-92 months after their treatment.
Dr. David Williams at Harvard’s Medical School reported the deaths. The seven boys were participants in the phase II/III ALD-102 and phase III ALD-104 trials. Results of the trial included approval of eli-cell to treat CALD that is active in boys ages 4-17 and the boxed warning urging caution for hematologic malignancies. Dr. Williams and his colleagues stated in the New England Journal of Medicine that the results of the studies suggest if any patients are considering the lentiviral gene therapy, as a follow through they should become familiar with its risks.
If treatment is selected, the patient should be monitored closely. Dr. Williams and his colleagues suggest that the conditioning agents used in the ALD-102 study (busulfan-cyclophosphamide) may potentially reduce cancer risk as opposed to agents (busulfan-fludarabine) that were used in ALD-104.
These boys were followed for approximately nine years through the LTF-304 study. Ninety-four were still alive at the 24th month while 81% showed no significant functional disabilities.
In an effort to provide adequate information, the NEJM report suggests that cancer-causing genetic mutations (oncogenesis) treated with eli-cell be compared against CALD’s history and include the risks associated with other treatments. This would also involve stem cell transplants.
