Mark Walters, MD, on Long-Term Blood Cancer Risk in Children Treated With Gene-Edited Cell Therapy


The professor in residence of pediatrics at University of California San Francisco discussed a potential long-term consequence of gene therapy and myeloablative conditioning.

“The most concerning safety question is whether or not going through a gene therapy treatment like this might increase the risk of developing a blood cancer, like acute myelogenous leukemia (AML). And we tend to worry about that more in the youngest patients because their lifespan will be longer and will perhaps have more potential for developing leukemia than in the older patients.”

The first gene therapy for the potential treatment of sickle cell disease (SCD) is up for review by the FDA with a Prescription Drug User Fee Act (PDUFA) date of December 20, 2023.1While the possible approval of lovotibeglogene autotemcel (lovo-cel; bluebird bio) has the potential to transform the treatment landscape of SCD, such a change comes with its own challenges and questions, and more research will be ongoing to address these.

CGTLive spoke with Mark Walters, MD, professor in residence, pediatrics, Sickle Cell Center of Excellence, University of California San Francisco, an investigator on the phase 1/2 HGB-205 (NCT02151526) and HGB-206 (NCT02140554) clinical trials evaluating lovo-cel, to learn more about the impending possible change to the treatment landscape and concerns the possible approval would bring about. Walters listed the potential long-term consequence of developing hematological malignancies, especially in children receiving the myeloablative conditioning and gene-edited cell therapy treatment. What makes the concern especially topical is the incidence of AML and myelodysplastic syndrome during the beginning of the HGB-206 trial under different study protocols when lovo-cel was known as LentiGlobin, later found unlikely to be due to the therapy’s lentiviral vector.

1. bluebird bio confirms that FDA has communicated that advisory committee meeting will not be scheduled for lovo-cel gene therapy for sickle cell disease. News release. bluebird bio. August 16, 2023.
2. bluebird bio provides updated findings from reported case of acute myeloid leukemia (AML) in LentiGlobin for sickle cell disease (SCD) gene therapy program. News release. bluebird bio. March 10, 2021. Accessed October 23, 2023.
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