Researchers at the Center for Cell and Gene Therapy at Baylor College of Medicine, Texas Children’s Hospital, and Houston Methodist Hospital report that cancer patients who receive treatment with genetically modified immune cells (IECs) are not at increased risk for subsequent malignancy when compared to patients who receive standard chemotherapy. Their study “Long-Term Follow-up for the Development of Subsequent Malignancies in Patients Treated with Genetically Modified IEs” appears in the journal Blood.

“Subsequent malignancies are well-documented complications in long-term follow-up of cancer patients. Recently, genetically modified IECs have showed benefit in hematologic malignancies and are being evaluated in clinical trials for solid tumors. While the short-term complications of IECs are well described, there is limited literature summarizing long-term follow-up, including subsequent malignancies,” the investigators wrote.

“We retrospectively reviewed data from 340 patients treated across 27 investigator-initiated pediatric and adult clinical trials at our center. All patients received IECs genetically modified with gamma-retroviral vectors to treat relapsed and/or refractory hematologic or solid malignancies. In a cumulative 1,027 years of long-term follow-up, 13 patients (3.8%) developed another cancer with a total of 16 events (four hematologic malignancies and 12 solid tumors).

“The five-year cumulative incidence of a first subsequent malignancy in the recipients of genetically modified IECs was 3.6% (95% CI: 1.8%-6.4%). For 11 of the 16 subsequent tumors, biopsies were available, and no sample was transgene positive by PCR. Replication competent retrovirus testing of peripheral blood mononuclear cells was negative in the 13 patients with subsequent malignancies tested. Rates of subsequent malignancy were low and comparable to standard chemotherapy.

“These results suggest that the administration of IECs genetically modified with gamma retroviral vectors does not increase the risk for subsequent malignancy.”

“While the short-term complications of IECs are well described, there have not been large-scale studies summarizing long-term follow-up, including subsequent malignancies,” said David Steffin, MD, co-first author of the study, assistant professor of pediatrics–hematology and oncology at the Center for Cell and Gene Therapy at Baylor and pediatric hematologist at Texas Children’s. “This is one of the largest studies of its kind, and our findings reinforce the long-term safety profile of genetically modified IECs.”

Thirteen patients in the cohort developed 16 secondary cancers in the months or years following treatment, a rate comparable to patients who receive standard-of-care therapies including chemotherapy and hematopoietic stem cell transplant. Researchers reviewed biopsy results for 11 of the secondary tumors and found no transferred genetic material from the therapy. All 13 patients tested negative for replication competent retrovirus at time of diagnosis.

“With the increased use of cell and gene therapy, some literature has discussed a potential risk for the genetically modified component of cells to integrate into genetic material of patients, leading to future risk of genetic mutations that could increase the risk for secondary malignancies. We found that did not happen in this patient cohort,” noted Ibrahim Muhsen, MD, co-first author of the study, chief medical resident at Houston Methodist, and an incoming hematology and oncology fellow at Baylor.

The authors stressed that patients treated with genetically modified IECs still should be considered a high-risk population and monitored closely with routine cancer screenings. The researchers said future studies will be necessary to determine the risk for other long-term complications like cardiotoxicity.