Guy's Cancer Center London, London, United Kingdom
G. Mikhaeel1,2, C. Bourlon3, D. Springell4, C. Roddie5, J. L. Brady2, M. Correia De Farias3, R. Sanderson6, R. Benjamin6, A. Hwang4, S. Kamat3, K. Courtney3, P. Patten6, E. Kumar3, P. Hardefeldt3, D. Yallop3, G. Ntentas7, K. Keshwani8, S. Sivabalasingham8, and A. Kuhnl9; 1School of Cancer and Pharmaceutical Sciences, Kings College London, London, United Kingdom, 2Guys and St Thomas NHS Foundation Trust, London, United Kingdom, 3Kings College Hospital NHS Trust, London, United Kingdom, 4University College London Hospital NHS Trust, London, United Kingdom, 5University College London Hospital NHS Trust, london, United Kingdom, 6Kings College NHS Trust, London, United Kingdom, 7Department of Medical Physics and Clinical Engineering, Guy´s and St Thomas´ Hospital, London, United Kingdom, 8Proton Beam Therapy Centre, University College London Hospitals NHS Trust, London, United Kingdom, 9Kings, London, United Kingdom
Purpose/Objective(s): Radiotherapy is an accepted bridging prior to CD19 CAR T in large B cell lymphoma (LBCL) and is sometimes used post CAR T for residual disease. However, consolidation (cRT) is not well established and there is no agreed standard for patient selection, timing, doses or techniques. Concern also exists regarding effect on circulating CAR T in responding patients. We initiated a prospective protocol for the use of RT with CAR T to: (1) standardize the selection of patients, (2) promote the use of RT consolidation post CAR T according to pre defined criteria, and (3) optimize the use of CAR T sparing RT in the consolidation setting. Materials/
Methods: The eligibility criteria included LBCL patients approved for CD19 CAR T and no contraindication for RT. Patients were selected for pathway A (Bridging RT alone) if most sites of disease can be covered with RT. Pathway B (bridging systemic therapy ± cRT) was selected for rapidly progressing disease, wide-spread extranodal disease (e.g. liver, lung, bone, peritoneum) or LDH >2xULN. Baseline PET CT was reviewed and sites at high risk for local recurrence (=5cm or SUVmax =15) were recorded. cRT post CAR T was given to high-risk lesions which on D28 PET CT showed a Deauville score (DS) 3-4 or 5 (but partial response). RT was planned 6-8 weeks post CAR T, with CAR T sparing technique. Results: 28 patients were entered between Nov 2021 – Oct 2023, 10 in pathway A & 18 in pathway B. Median age was 55 years. 51.7% had stage 4 (20% vs. 68.4% in A vs. B). 44.8% had bulky disease, 24.1% =2 extranodal sites, and 48.2% high LDH. 1 patient in pathway A did not receive CAR T due to PD. RT dose was 20-36Gy (10-12#) in pathway A, all delivered with VMAT and with no gaps. Pathway B doses were 25-37.5Gy / 5-15# (23/26 sites treated with VMAT) and with no gaps. Planning modifications for early cRT post CAR T included: (1) contouring and dose-optimisation of blood vessels (BV) and blood-rich OARs (BR-OAR) to reduce doses to blood, and (2) measures to reduce beam-on time to account for the circulating nature of blood; hypofractionation (2.5 – 5 Gy/#, median = 3), limited beam angles (e.g. partial single arcs) avoiding BV and BR-OAR, and flattening filter free (FFF) beams. Overall response rate at 1 month was 86.2% (41.4% DS 1-3) and 48.2% at 6 months. With a median follow-up of 180 days, 9 patients progressed (4 in pathway A and 5 in pathway B) and 5 died, all due to disease progression. Data on local disease control, progression-free and overall survival will be provided at the meeting. Significant toxicity included 2 G3 ICANS but no CRS G= 3. No G=3 toxicity reported after cRT. Conclusion: Implementing a comprehensive protocol of RT bridging and post CAR T RT consolidation with selection of patients based on pre-defined criteria was feasible. All patients but one completed treatment according to protocol. The disease control outcomes and the toxicity are promising, particularly in the RT consolidation setting.
