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Radiation therapy before CART-BCMA infusion is safe and doesn't interfere with cellular therapy


Administering radiation therapy to multiple myeloma patients waiting for CAR T cells to be manufactured was found to be safe and undisruptive to CAR T therapy, according to a new study from researchers in the Abramson Cancer Center at the University of Pennsylvania.

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

Radiation for relapsed / refractory multiple myeloma is often used to palliate bone pain associated with the disease; however, what effect it may have on patients and CAR T cell therapy hasn't been fully understood.
The new findings suggest it 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.

Chimeric antigen receptor T cell therapy, known as CAR T, is an investigational treatment pioneered by researchers at Penn that modifies patients' own immune T cells, which are collected and reprogrammed to seek and destroy the patients' cancer cells.
After being infused back into patients' bodies, these newly built hunter cells both multiply and attack.
The Penn-developed CART-BCMA targets cells that express BCMA, which is highly expressed in myeloma.

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

None of the four patients who received radiation while awaiting manufacturing experienced CRS, gastrointestinal, infectious, liver-related, or neurologic toxicities higher than a grade 3.

Cytokine release syndrome is a toxicity that includes varying degrees of flu-like symptoms, with high fevers, nausea, and muscle pain, and can require ICU-level care.
Those patients also had lower rates of grade 4 hematologic toxicities.
Of the eight patients who had a prior history of radiation, three experienced grade 3 or higher cytokine release syndrome.
Among the 13 patients who did not receive any radiotherapy, five experienced grade 3 or higher cytokine release syndrome.
Radiation status was not associated with a decrease in overall survival or progression free survival.

In 2019, Penn researchers presented findings at ASTRO that found radiation did not interfere with the efficacy of CAR T cell therapy in non-Hodgkin lymphoma and had the potential to lower side effects in these patients. ( Xagena )

Source: American Society for Radiation Oncology ( ASTRO ) Virtual Meeting, 2020

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