Study Supports Use of Radiation Before CAR-T Cell Therapy for Multiple Myeloma

The study found patients who received radiation 34 days or fewer before their infusion with CART-B cell maturation antigen (BCMA) cells did not have worse rates of severe cytokine release syndrome or neurotoxicity, which are 2 common adverse effects of the cellular therapy.

A new study from researchers in the Abramson Cancer Center at the University of Pennsylvania found that administering radiation therapy to patients with multiple myeloma who are waiting for chimeric antigen receptor (CAR) T cells to be manufactured is safe and undisruptive to CAR T-cell therapy.

The study found patients who received radiation 34 days or fewer before their infusion with CART-B cell maturation antigen (BCMA) cells did not have worse rates of severe cytokine release syndrome or neurotoxicity, which are 2 common adverse effects of the cellular therapy. Further, the patients did not have worse hematologic toxicities than patients who did not have bridging care.

These new findings suggest that radiation appears to be a safe option for patients before they receive their CAR T-cell infusions, lending more support for future studies that combine radiation with cellular therapy, according to the study authors.

“The most important takeaway here is that bridging radiation doesn't appear to increase the risk of CRS or neurotoxicity," said lead author Shwetha Manjunath, MD, a resident in radiation oncology in Penn's Perelman School of Medicine, in a press release. "These patients safely received bridge radiation without it affecting the efficacy of CAR T cells or the rates of toxicity."

The study evaluated the medical records of 25 patients who received CART-BCMA and categorized them into 3 groups. One group received radiation after their cells were collected for CAR T-cell manufacturing, but before infusion, at a period of 34 days or less. The second group of patients had received radiation within 1 year prior to CAR T-cell infusion. Lastly, the third group received either no radiation at all or no radiation within the year preceding CAR T-cell infusion.

None of the 4 patients who received radiation while awaiting manufacturing experienced CRS, gastrointestinal, infectious, liver-related, or neurologic toxicities higher than a grade 3. Further, these patients also had lower rates of grade 4 hematologic toxicities.

Of the 8 patients who had a prior history of radiation, 3 experienced grade 3 or higher CRS, and radiation status was not associated with a decrease in overall survival or progression free survival.

"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," Manjunath said in a press release. "Future prospective trials that combine radiation with CART-BCMA may further optimize safety and long-term efficacy of this novel cell therapy."

REFERENCE

Penn study supports use of radiation before CAR therapy for multiple myeloma. EurekAlert! https://www.eurekalert.org/pub_releases/2020-10/uops-pss102520.php. Published October 26, 2020. Accessed October 28, 2020.