Addressing Adverse Outcomes and Enhancing Patient Care in Gene Therapy

Overcoming challenges and navigating unexpected adverse outcomes when using commercial gene therapies requires collaboration from across varying disciplines, health care institutions, and patient advocacy groups, with an effective multidisciplinary care team being key to managing the possible complications of gene therapies, according to an expert roundtable at the American Society of Transplantation and Cellular Therapy’s second annual Gene Therapy Summit, which took place on September 11, 2025, in Boston, Massachusetts.¹

Gene therapy requires careful coordination and collaboration across the care team. | Image Credit: © ipopba - stock.adobe.com

The roundtable discussion was chaired by Hemalatha Rangarajan, MD, Nationwide Children’s Hospital, and Rayne Rouce, MD, associate professor at Baylor College of Medicine and pediatric oncologist at Texas Children’s Hospital.¹

Panelists included Colleen Dansereau, MSN, RN, CPN, vice president of emerging discoveries at Boston Children's Hospital; David Jacobsohn, MD, SCM, MBA, chief of the blood and marrow transplantation program at Children's National Hospital; John Tisdale, MD, chief of the cellular and molecular therapeutics branch of the National Heart, Lung, and Blood Institute; Mark Leick, MD, assistant professor of medicine, Massachusetts General Hospital Cancer Center; and Kathleen O'Sullivan-Fortin, Esq., co-founder of ALD Connect and member of the FDA Cellular, Tissue, and Gene Therapy Advisory Committee.¹

Taking questions from both the audience and Rangarjan and Rouce, the experts tackled a variety of topics, including the need for standard operating procedures and preparedness for unexpected outcomes, ensuring families and patients are supported, and the role of pharmacists in the multidisciplinary care team. Above all, the experts emphasized that the challenges addressed during this session—and the Gene Therapy Summit as a whole—can be solved with teamwork and a patient-first perspective.¹

Importance of Multidisciplinary Collaboration

Throughout the summit, experts from throughout the health care spectrum emphasized a common goal of working across disciplines to ensure a patient with a hematologic malignancy receives the best possible care. As part of that team, pharmacists play a vital role. Through helping set up standard operating procedures (SOPs) for mobilization, determining the timing of certain medications, and managing any allergic reactions or other adverse events (AEs), the experts agreed that pharmacists were integral in counseling patients undergoing gene therapy who may experience adverse outcomes.¹

Furthermore, pharmacists are integral in timing plerixafor (Mozobil; Sanofi) doses, a critical component of stem cell mobilization prior to autologous hematopoietic cell transplant for hematologic malignancies. Sometimes, a standard dose of plerixafor is insufficient at mobilizing cells into peripheral blood for collection, and providers may encounter challenges regarding the short time frame between mobilization and collection, which can be as short as 3 hours in sickle cell disease.^1,2

“We have disease-modifying therapy pharmacists and numerous others, and I think they’re very, very important,” Jacobsohn said during the discussion. “A lot of the SOPs for mobilization have been developed with their input. I think they’re a vital part of the care team.”¹

Rangarajan discussed how many gene therapy SOPs are developed dynamically, meaning that as new outcomes or possible AEs are observed—including pneumonitis or injury to the lung—pharmacists can communicate with the team to ensure they are accounted for in the future. Pharmacists also are essential in monitoring pharmacokinetics during gene therapy, and through consultation and follow-up with the patient, can provide insights to members of the team as to how a mobilization agent or gene therapy injection is affecting the body over time—and provide proper strategies to ameliorate any complications.^1,2

“We’re constantly looking at and learning from each other,” Rangarajan explained. “I think the pharmacist’s role is very vital, and they keep us in check. Always.”¹

Preparing for the Unexpected

As mentioned, SOPs are a critical component of ensuring preparedness and common procedures in the case of unexpected outcomes in gene therapy. However, the panelists agreed that sometimes, the fast-moving reality of gene therapy infusion requires fluidity and “making changes on the fly,” especially in the sickle cell space, according to Tisdale. He cited an example of a patient that had to have platelet thresholds adjusted based on early observations of central nervous system bleeding. Now, at his center, more platelets are requested before infusion begins, in the case of any adjustments.¹

Jacobsohn echoed this sentiment, citing earlier examples of a patient who experienced an allergic reaction to a mobilization agent and another who experienced a seizure in the outpatient setting. “A network to learn about these cases in real time is critical,” he explained.¹

Dansereau described how the gene therapy field is “a fluid space” that requires innovation for operationalizing and optimizing therapies. Accordingly, O’Sullivan-Fortin highlighted the importance of involving and educating patients along the way, noting that any outcome—whether it is expected or unexpected on the parts of the investigators and health care providers—can be scary and unknown for patients. In this vein, Tisdale explained how, in his practice, they are upfront with the patient from the very beginning of the journey.¹

“You have to be a good doctor,” Leick said, saying that providers should take commonsense steps to evaluate for novel toxicities, while “talking to colleagues and keeping an eye on literature” remain critical.¹

Supporting Families and Integrating Patients

O’Sullivan-Fortin, representing the patient advocacy end of gene therapy, stressed the importance of consistent patient education and representation in their treatment journey. She particularly noted the dangers of rapidly spreading information in patient communities through social media, which could add greater mental strain to patients who may already be confused or afraid regarding their prognosis.¹

“It doesn’t matter how beautifully they are during the process of consent; all the information that comes out is like a fire hose,” O’Sullivan-Fortin said. “Really realizing that, even though several people in your team may have assured them that this is normal or foreseeable—or maybe not—they will still have heard it again if it happens to their loved one and their child. From a patient perspective, it is both a challenge and a gift that patient communities are so galvanized online.”¹

Ultimately, O’Sullivan-Fortin acknowledged that “we are stronger together.” During this discussion, Rouce expressed gratitude for the experts tackling the issue of patient representation, explaining that “from a patient perspective, a provider perspective, and an operational perspective, we all have to be attuned to those kinds of things.”¹

Tisdale pointed out that, with such a big emphasis on patient support, such processes need to begin earlier to build trust over time. Patients with sickle cell disease, who may harbor distrust when it comes to curative therapies, need to begin the consent and support process earlier to account for the possibly long period until gene therapy can begin. Jacobsohn reiterated this point, noting that it’s “a process and really a team effort” that requires adaptation for each patient and their families.¹

REFERENCES

1. Rangarajan H, Rouce R, Dansereau C, Jacobsohn D, Tisdale J, et al. “Managing Unexpected and Adverse Outcomes Roundtable.” Presented: American Society of Transplantation and Gene Therapy 2025 Gene Therapy Summit. September 11, 2025. Joseph B. Martin Conference Center, Boston, Massachusetts.

2. Halpern L. Navigating the Complex Landscape of Sickle Cell Gene Therapy: Operational Challenges and Collaborative Solutions. Pharmacy Times. Published September 11, 2025. Accessed September 12, 2025. https://www.pharmacytimes.com/view/navigating-the-complex-landscape-of-sickle-cell-gene-therapy-operational-challenges-and-collaborative-solutions