Session Item

Patients with Large B-cell lymphoma (LBCL) who have refractory or relapse disease after two lines of systemic therapy (ST) have a very poor prognosis. However, for these patients anti-CD19 chimeric antigen receptor T-cell (CART) therapy has emerged as a potential curative treatment regime as approximately half of the patients achieve long-term disease-free survival. CAR T-cells are generated from autologous T-cells, collected through an apheresis procedure. The logistics and production are time consuming and may take up to 4-6 weeks.

Many patients in which CART therapy (CARTT) is indicated have symptomatic and progressive disease during the production period. Bridging therapy, referred to therapy administered after apheresis until CART infusion may be indicated. Early reports on radiotherapy (RT) as a bridging strategy have shown feasibility, safety and effectivity, but patient numbers were limited.

Here we present our experience with bridging in patients selected for CART therapy in a relatively large cohort. The current analysis focuses on the evaluation of the response rates.

All patients treated with CARTT are included in a prospective data registration program including data on patient and tumor characteristics, treatment, toxicity and outcomes. For this analysis all patients with LBCL who underwent apheresis for CARTT were included. Bridging therapy may consist of steroids, chemotherapy, RT or a combination of these treatments. Responses to bridging therapy were based on ¹⁸F-Fluordeoxyglucose PET (FDG-PET) before CARTT and survival outcomes are reported.

In total 45 patients underwent an apheresis procedure. Fourteen of these patients (31.1%) did not receive bridging treatment, 19 (41.2%) underwent RT alone, 5 (11.1%) received ST alone (steroids or chemotherapy) and 7 (15.6%) received ST and RT (See table). RT was given on bulky tumor or burdensome lesions, in the majority of patients to a total dose of 20 Gy in 5 fractions (See figure). Eighty-one percent of patients had an infield response to RT. All patients who received RT alone had out of field progression, compared to 87% in patients who received RT and ST and 66% in patients after ST alone.

Finally 41 patients (91.1%) received CARTT, while 3 patients did not due to rapid progression and no residual disease (1). The 1-year overall survival of patients who did not receive bridging treatment was 90%, compared to 74.1% in patients bridged with RT alone and 46.7% in patients treated with ST or combined treatment. 1-year progression free survival was 62.3% versus 48.9% and 40.0%, respectively.

Bridging the time between apheresis and infusion is a critical phase in CARTT. Selection of bridging treatment type is based on prior treatment, tumor load and symptoms. RT is a good alternative for ST in this heavily pre-treated patient population with a control rate of 81%. Given the high progression rate, close follow-up is needed during the bridging phase.