Is Radiation Safe as a Bridging Strategy to CAR T Therapy in Advanced DLBCL?

Radiation therapy-either with or without concurrent chemotherapy-may be a safe bridging therapy for patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) during the interval between collection of autologous T cells and final CAR T administration, according to data from a case series published in the International Journal of Radiation, Oncology, Biology and Physics.

During the bridging treatment with radiation, no patients experienced significant toxicity or in-field disease progression of disease.

“In this cohort of patients in whom no effective systemic therapy was available, bridging radiation was able to safely bridge patients to [axicabtagene ciloleucel] therapy with outcomes after CAR T comparable to patients treated in recent clinical trials,” wrote Austin J. Sim, MD, JD, of Moffitt Cancer Center, and colleagues.

According to the study, bridging therapy may be required in patients with relapsed or refractory DLBCL in order to control the lymphoma during the approximate 3 to 4 weeks between the collection of a patient’s T cells via apheresis and CAR T-cell infusion. The goal of bridging therapy is to debulk the tumor and maintain performance status until CAR T cells can be delivered.

“Significant time typically elapses between identifying recurrent or refractory disease and CAR T infusion,” the researchers wrote. “This can include the time needed to refer to a CAR T treatment center for evaluation, approval by insurance, manufacturing of CAR T cells after collection (3 to 4 weeks), shipping, and conditioning chemotherapy. As a result, effective bridging strategies may be needed to provide patients with aggressive disease access to CAR T therapy.”

This small case series included 12 patients intended to receive radiation as bridging therapy from December 2017 to October 2018 prior to axicabtagene ciloleucel. All included patients had aggressive disease, including 6 patients with double hit lymphoma and 6 patients with disease 10 cm or larger in diameter.

Patients received between 2 Gy and 4 Gy per fraction to a median dose of 20 Gy. Half of the patients received either 30 Gy in 10 fractions or 20 Gy in 5 fractions. Seven of the 12 patients had concurrent chemotherapy.

One patient did not get infused. The patient had out-of-field progressive disease after apheresis and radiation, and because of declining performance status, refused infusion.

During bridging radiation, no significant toxicities were reported. One patient had abdominal pain, but symptoms were resolved with dose reduction. No patient had in-field progression of disease prior to axicabtagene ciloleucel. Out-of-field progression occurred in two patients during the bridging therapy.

After CAR T-cell infusion, 27% of patients had severe cytokine release syndrome or neurotoxicity.

At 30 days, the objective response rate was 81.8% with 27%, or 3 of 11 patients, achieving complete response. At the last follow-up, best objective response rate was 81.8%, with complete response attained in 5 of 11 patients (45%).

Another researcher on the study, Frederick Locke, MD, of Moffitt Cancer Center, told Cancer Network that he believes this strategy could be widely adopted at centers giving CAR T-cell therapy.

“We treated these patients with radiation to bridge them to the CAR T-cell therapy and we found that it was safe to do so, and that the outcomes were no worse following CAR T-cell therapy,” Locke said. “We think this is an important finding and that it may be useful for patients undergoing this therapy.”

Locke noted that more studies are needed to more fully understand the effects of radiation and other bridging strategies on the outcomes of CAR T-cell therapy.