Subsequent malignancies were well-documented consequences in cancer patients with long-term follow-up. Recently, genetically modified immune effector (IE) cells have shown efficacy in hematologic malignancies and are being tested in solid tumor clinical trials. However, while the short-term problems of IE cells were widely documented, there was little research describing long-term follow-up, including future cancers. For a study, researchers assessed data from 340 patients treated at their facility in 27 investigator-initiated pediatric and adult clinical studies.
To treat recurrent and/or refractory hematologic or solid cancers, all patients were given IE cells that had been genetically transformed with γ-retroviral vectors.
In a total of 1,027 years of long-term follow-up, 13 patients (3.8%) acquired additional cancer, resulting in 16 incidents (4 hematologic malignancies and 12 solid tumors). In recipients of genetically modified IE cells, the 5-year cumulative incidence of a first subsequent cancer was 3.6% (95% CI, 1.8% to 6.4%). Biopsies were obtained for 11 of the 16 following tumors, and no sample tested positive for the transgene by polymerase chain reaction. The 13 individuals with future malignancies had their peripheral blood mononuclear cells tested negative for replication-competent retroviruses. Following malignancy rates were modest and equivalent to normal treatment.
The findings indicated that administering IE cells that have been genetically transformed with γ-retroviral vectors does not raise the risk of future cancer.