Radiation Does Not Disrupt CAR T-Cell Therapy in Patients With MM, Study Finds

Patients with multiple myeloma (MM) can safely undergo radiation therapy without disrupting their plan to receive chimeric antigen receptor (CAR) T-cell therapy, according to new research. The study, presented last month at the American Society for Radiation Oncology’s annual meeting, was conducted online due to the coronavirus disease 2019 pandemic.

CAR T-cell therapy has increasingly been seen as a potential breakthrough treatment for patients with MM, as well as other types of cancers. The therapy involves reprogramming patients’ own immune cells before infusing them back into the patients, where they find and kill cancer cells.

The new study focuses on CAR T B-cell maturation antigen (CART-BCMA) treatment, which was developed at the University of Pennsylvania.

Shwetha Manjunath, MD, the study’s lead author and a resident in radiation oncology at Penn’s Perelman School of Medicine, said in a press release that although radiation has long been used to help alleviate bone pain associated with relapsed or refractory MM, it was not known whether the therapy could be safely and effectively used in patients who would eventually go on to undergo CAR T-cell therapy.

To study this question, Manjunath and colleagues retrospectively identified 25 patients who received CART-BCMA therapy. Those patients were categorized into one of 3 groups:

1. Those who received radiation therapy between the time cells were collected for CAR T-cell manufacturing and the therapy was administered (a time span of 34 days or less)
2. Those who received radiation within 1 year before their CAR T infusion
3. Those who received no radiation in the year prior to receiving CAR T-cell therapy (if at all).

The first group consisted of 4 patients. None of these patients experienced severe adverse effects like cytokine release syndrome (CRS) or grade 3 or higher gastrointestinal, infectious, liver-related, or neurological toxicities. Those patients also had lower rates of grade 4 hematologic toxicities, the authors said.

Among the 8 patients who had previous radiation, 3 experienced grade 3 or higher CRS. The remaining 13 patients, none of whom had undergone radiation in the year prior to CAR T-cell infusion, had 5 cases of grade 3 or higher CRS.

The authors found no decrease in overall survival or progression-free survival among the patients who underwent radiation.

“The most important takeaway here is that bridging radiation doesn’t appear to increase the risk of CRS or neurotoxicity,” said Manjunath, in a press release. “These patients safely received bridge radiation without it affecting the efficacy of CAR T cells or the rates of toxicity.”

In fact, Manjunath said it may well be that radiation therapy actually helps the efficacy of CAR T-cell therapy.

“Our work is hypothesis generating, hinting at a potential synergism between radiation and CART-BCMA therapy, which has been reported by others in the literature,” she said, adding that future prospective trials of radiation and CART-BCMA are warranted to better understand the safety profile and long-term efficacy of the combination.

Reference

Manjunath SH, Cohen AD, Arscott WT, Maity A, Plastaras JP, Paydar I. Is bridging radiation (RT) safe in B cell maturation antigen-targeting chimeric antigen receptor T cells (CART-BCMA) therapy? Int J Radiat Oncol Biol Phys. 2020;108(suppl 3):S165-S166. doi:10.1016/j.ijrobp.2020.07.934