Monitoring Patients After Gene Transfer Therapies Is an Important Link in the Chain of Neuromuscular Care

Gene transfer therapies have improved the odds of living a life with reduced or no disability for many patients with neuromuscular disorders (NMD). While adeno-associated virus (AAV) vectors are considered relatively safe vehicles for the infusion of gene therapies, they are delivered systemically in very high doses, which may put major organs at risk.

The optimal management of patients with NMDs who receive gene therapy infusions involves careful institutional planning, education of caregivers and clinical teams, and coordination of care, said Diana Bharucha-Goebel, MD, Director of the Muscular Dystrophy Association clinic at Children’s National Hospital in Washington, D.C.

Clinicians should become familiar with the potential safety issues following gene transfer and the drivers of immune response. Many variables affect immune responses in patients who receive gene therapies, Bharucha-Goebel explained in a session at the 2024 MDA Conference. These include total vector genome dose, vector purity, type of prophylactic immune regimen, genotype, host susceptibility, and cytotoxic immune response. “There are many different factors that can increase or mitigate the risks through those immune responses,” Bharucha-Goebel said. “Not all gene therapy products or populations are going to be the same. We have to always be on high alert and think of each one differently in terms of our growing knowledge in this area.”  

Before the gene transfer is initiated, clinicians should familiarize themselves with the timeline and the types of immune responses reported in clinical trials and prepare for possible adverse events. This could help determine the type of laboratory tests required for optimal monitoring, the length of monitoring post-gene transfer, and help with the interpretation of shifts in laboratory values or emerging laboratory abnormalities. “These are things we want to know as clinicians when we are developing institution guidelines for a new product,” the speaker said. “We may even modify them if we start seeing divergent experiences post transfusing the approved therapy.”  

Clinicians face uncertainty, especially in the early days after the transfer, when laboratory abnormalities may be hard to decipher in the context of individual immune responses to therapy. “Knowing what we know and what we do not yet know, how can we make gene therapy safer and improve our practices?” Bharucha-Goebel asked. “It takes a lot of people, a broad team. Communication and coordination of the care, both with your team and with the family, is key.”  

In the days leading up to the gene infusion, the clinical team must evaluate all safety parameters relating to the patient’s condition, eligibility, baseline laboratory values, cardiac imaging, and other studies, as needed. “Recurrent counseling is important,” the speaker said. “Make sure that the family understands the critical nature of the need for close monitoring. Another thing to think about are obstacles to frequent visits around work and school schedules. Think about how to help the family through what is a very intense period.”  

As the day of the gene transfer draws closer, the clinical team must recheck laboratory values, ensure that there are no recent infections or immunizations, and initiate prophylactic corticosteroid regimens. It is important to maintain communication with the patient’s primary care provider throughout this process, the speaker noted. Before the infusion is initiated, clinicians must confirm that the family has consented to the therapy and that prednisone was administered as directed before the procedure. Once the intravenous line is in place, the pharmacy can be notified to prepare and hand deliver the gene therapy product.

After the infusion is completed, the patient should be monitored for 4 to 6 hours. Clinically stable patients can be discharge to home. However, the family should receive a roadmap that clearly lays out the follow-up visits with the neuromuscular team and other specialists. The clinical chart should include an alert about gene therapy protocol to notify the relevant hospital teams in case the patient presents to the emergency department.  

Following the gene transfer, pediatric patients should be seen by the primary care provider within 1 to 2 days for a vital sign check, followed by a visit with the neuromuscular care team within 72 hours. Patients who show signs of dehydration should be referred to the emergency department. Basic laboratory values and motor function should be measured 3 months post-therapy and at least every 3 months for the first year. Ideally, multidisciplinary follow-up should be performed twice a year, Bharucha-Goebel said, noting that clinicians should identify and report adverse events. “There is a need to share clinical experiences, common as well as atypical adverse events, emerging trends, and treatment or mitigation strategies that are being used by clinicians, researchers, and sponsors to optimize safety for individuals receiving gene therapy,” the speaker concluded.