2921 - Phase II Study of Low Dose Bridging Radiotherapy prior to Axicabtagene-Ciloleucel in Patients with Relapsed/Refractory Follicular Lymphoma

Purpose/Objective(s):

Follicular lymphoma (FL) is considered an indolent non-Hodgkin lymphoma; however, it is characterized by a relapsing-remitting course, typically with decreasing response duration with subsequent lines of therapy. Use of anti-CD19 chimeric antigen receptor (CAR) T-cell therapy in patients (pts) with FL has been limited due to treatment intensity and toxicity. Among FL pts enrolled on Zuma 5, grade 3 or higher cytokine release syndrome (CRS) was seen in 6% of pts, while grade 3-4 neurologic events were seen in 15% of pts. As FL is highly radiosensitive, we hypothesize that bridging RT (bRT) prior to axicabtagene-ciloleucel (axi-cel) will provide effective cytoreduction and limit high grade CRS and immune effector cell-associated neurotoxicity syndrome (ICANS) while maintaining efficacy.

Materials/Methods:

We conducted a single-arm phase II study of pts with relapsed/refractory (R/R) FL planned for standard-of-care axi-cel with bRT. Five pts have been enrolled to date. Following apheresis, all pts received 4 Gy in 2 fractions of near-comprehensive bRT, defined as omission of 1 disease site selected at physician discretion. Responses were assessed using Lugano criteria. Steroids were permitted however other bridging systemic therapy was not. Toxicity was graded using CTCAE v5.

Results:

The median age at diagnosis was 55 years (IQR 53-62) (Table 1). Patients received a median of 3 prior lines of therapy (IQR 3-5), including bendamustine (3/5 pts) and mosunetuzumab (3/5 pts). Following bRT, patients experienced the following toxicities: grade 1 (G1) fatigue in 2/5 pts, G1 nausea in 2/5 pts, G3 hematologic toxicity in 2/5 pts. The median total metabolic tumor volume (TMTV) using SUV 2.5 decreased from 385.5 cc (IQR 160-1473cc) to 28.6cc (IQR 18.2-527.85cc) following bRT (p = 0.18).

Following axi-cel infusion, 4 pts experienced G1 CRS and 1 pt experienced G2 CRS. Median onset of CRS was 1 day (range 1-6 days) with median duration of 4 days (range 3-9 days). Three pts developed ICANS, which was grade 2 in two pts and grade 3 in one. Median onset of ICANS was 7 days (range 6-10) with median duration of 1 day (range 1-3). Median peak CAR-T expansion was 252 cells/microL (IQR 150-324) at a median of 9 days post-infusion (IQR 7-10).

All pts experienced a CR on D30 PET/CT following axi-cel. At a median follow-up of 9 months post CAR-T (IQR 3-16 months), 4/5 pts remain in CR. One pt has radiographic concern for in-field progression but has not undergone biopsy or started subsequent treatment.

Conclusion:

Axi-cel is an effective treatment option for pts with R/R FL. Bridging low dose RT is associated with manageable toxicity and may limit high grade CRS and ICANS, though further study is needed.

Table 1. Summary of disease and post-treatment characteristics

Pt #	Prior lines of therapy	TMTV prior to bRT (cc)	Response to bRT (5 PS)	TMTV after bRT (cc)	Max grade CRS	Max grade ICANS	Max CAR-T expansion (cells/uL)	D30 response (5PS)
1	4	2098	4	432	1	0	109	2
2	3	260	4	29	1	2	190	2
3	3	848	4	624	1	0	359	1
4	3	385	4	26	1	3	289	2
5	5	61	4	11	2	2	252	1