Administering radiation therapy to people with relapsed or refractory (resistant) multiple myeloma waiting for CAR T-cells to be manufactured was found to be safe and did not impact CAR T-cell therapy, a small study reports.
The study details were shared at the virtual 2020 American Society for Radiation Oncology (ASTRO) Annual Meeting, in a presentation titled “Is Bridging Radiation (RT) Safe with B Cell Maturation Antigen–targeting Chimeric Antigenic Receptor T Cells (CART-BCMA) Therapy?”
Chimeric antigen receptor (CAR) T-cell therapy is an investigational treatment in which a patient’s immune T-cells are collected and reprogrammed to better target and destroy cancer cells.
In multiple myeloma, this approach is often designed to target a protein called B-cell maturation antigen, or BCMA, which is found at high levels at the surface of myeloma cells, but minimally produced in healthy tissues.
After the engineering step, the cells are expanded to several million in the lab, and then infused back into the same patient.
Radiation therapy for people with multiple myeloma is often used for bone pain associated with the disease. However, whether radiation treatment impacts CAR T-cell therapy, especially when a patient is waiting for CAR T-cells to be manufactured, is not fully understood.
To find out, researchers at the University of Pennsylvania (UPenn) examined the medical records of 25 patients who received CAR T-cell therapy, including some who were also given radiation therapy before CAR T-cell infusion.
The team collected information on the radiation therapy, response, and toxicity, especially two common side effects from the cell-based treatment: neurotoxicity and severe cytokine release syndrome (CRS). CRS involves the rapid release of immune signaling proteins (cytokines) into the blood that may result in life-threatening symptoms.
Among the patients investigated, 13 — known as group 1 — received no radiation therapy within one year before CAR T-cell infusion. Meanwhile, eight patients, known as group 2, received radiation therapy within one year prior to CAR T-cell infusion, with a median time from radiation to cell collection of 88.5 days (ranging from 15 to 295 days).
The four individuals in group 3 were given so-called bridging radiation therapy — given after cell collection but before infusion — with a median time from cell collection to radiation of 17 days (ranging from 14 to 22 days) and from radiation to CAR T-cell infusion, a median of 34 days (ranging from 21 to 42 days).
The results revealed that the proportion of patients experiencing moderate CRS were comparable among all groups. In contrast, more severe CRS was slightly more common in those who did not receive radiation (38.5%) compared with the two groups that did (25%). Only one patient (12.5%) in group 2 experienced a life-threatening adverse event.
Neurotoxicity was low, with 7.7% of patients with no prior radiation reporting a severe grade 3 adverse event; 25% of those in both groups with radiation therapy reported severe grade 3 adverse events. Two life-threatening neurotoxicities were observed in group 2 only (25%).
The four patients who underwent bridging therapy had lower rates of blood-based (hematologic) toxicities (25%) compared with those who had no radiation therapy (61.5%) and radiation therapy within one year (62.5%). None of the bridging therapy subjects had moderate or worse gastrointestinal, infectious, or liver-related toxicities.
“The most important takeaway here is that bridging radiation doesn’t appear to increase the risk of CRS or neurotoxicity,” Shwetha Manjunath, MD, of UPenn’s Perelman School of Medicine and the study’s lead author, said in a press release.
“These patients safely received bridge radiation without it affecting the efficacy of CAR T cells or the rates of toxicity,” Manjunath said.
Whether a patient had radiation did not impact overall survival or progression-free survival, which is the time a person lives without signs of disease progression.
The response rates also appeared similar among the groups, despite the low number of patients examined. Among those without prior radiation, the response rate was 53.7% and the clinical benefit rate was 100%, meaning that all patients attained at least stable disease.
For individuals who received radiation therapy within one year, 37.5% had a partial or complete response to treatment, and their clinical benefit rate was 62.5%.
Finally, for those given the bridging therapy, 50% had a partial response, and the remaining half (two patients) showed a minimal response, amounting to a 100% clinical benefit rate.
“Our results suggest that bridging [radiation therapy] is safe and feasible without worsening rates of severe CRS, neurotoxicity, or hematologic toxicity,” the investigators concluded.
The research group at UPenn had presented data at last year’s ASTRO meeting that also found radiation therapy did not impact the efficacy of CAR T-cell therapy in non-Hodgkin’s lymphoma patients and may lower side effects.
“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. “Future prospective trials that combine radiation with CART-BCMA may further optimize safety and long-term efficacy of this novel cell therapy.”
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