1119 - Normalization of Lactate Dehydrogenase (LDH) as a Potential Prognostic Factor for Relapsed/Refractory Aggressive B-Cell Lymphoma (R/R BCL) Patients Receiving CAR T Following Bridging Radiotherapy: Res

M. Chelius¹, N. Yegya-Raman², J. Baron¹, M. D. Jain³, J. Yahalom⁴, B. S. Imber⁵, S. V. Dandapani⁶, C. J. Ladbury⁶, P. Fang⁷, S. Y. Wu⁷, S. E. Braunstein⁸, J. Chew⁸, A. J. Sim⁹, S. A. Terezakis¹⁰, G. Sakthivel¹¹, Y. D. Tseng¹², J. P. Plastaras², E. A. Chong¹³, N. B. Figura⁹, and H. G. Hubbeling¹⁴; ¹Department of Radiation Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA, ²Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, ³H. Lee Moffitt Cancer Center and Research Institute, Department of Blood and Marrow Transplant and Cellular Immunotherapy, Tampa, FL, ⁴Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, ⁵Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, ⁶Department of Radiation Oncology, City of Hope National Medical Center, Duarte, CA, ⁷Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, ⁸Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, ⁹H. Lee Moffitt Cancer Center and Research Institute, Department of Radiation Oncology, Tampa, FL, ¹⁰University of Minnesota: Department of Radiation Oncology, Minneapolis, MN, ¹¹50 CHESTNUT ST, ROCHESTER, NY, ¹²Department of Radiation Oncology, University of Washington/ Fred Hutchinson Cancer Center, Seattle, WA, ¹³Department of Medicine, Division of Hematology/Oncology, University of Pennsylvania, Philadelphia, PA, ¹⁴Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA

Purpose/Objective(s):

Elevated LDH is associated with inferior outcomes for R/R BCL patients (pts) receiving chimeric antigen receptor T cells (CAR T). We assessed the proportion of pts who experience LDH normalization following bridging radiotherapy (BRT) and prognostic implications. Materials/

Methods: We retrospectively analyzed 172 pts across 10 institutions who received BRT prior to CAR T from 2018-2020. LDH was collected both prior to leukapheresis (preBRT) and prior to CAR T infusion (postBRT) and classified as “Hi” or “Lo” based on institutional upper limits of normal. Pts were categorized into 4 groups: HiHi, HiLo, LoHi, and LoLo, based on their two respective LDH values. Progression-free survival (PFS) and overall survival (OS) were calculated from CAR T infusion using the Kaplan-Meier methods and modeled using Cox regression.
Results: Baseline characteristics were as follows: median age 62, 74% female, 71% diffuse large B cell lymphoma, 74% advanced stage, 39% bulky disease (=10cm), 66% elevated preBRT LDH, 44% elevated postBRT LDH. 39% of pts received comprehensive BRT and 23% received systemic bridging. Of those with initially elevated LDH, 39% experienced normalization postBRT. Those with HiLo LDH had similar PFS and OS to those with LoLo LDH (p=0.42; p=0.64, respectively), and better PFS and OS compared to those with HiHi (p < 0.001; p<0.001, respectively) and LoHi (p=0.002; p<0.001, respectively). Complete response (CR) rates differed between cohorts (p < 0.001), with superior CR rates in HiLo and LoLo groups. Excluding pts who received systemic bridging, the PFS and OS differences across LDH subgroups were maintained (Table 1). Cytokine release syndrome grade 3+ events were low among all groups and neurotoxicity occurred less frequently among HiLo and LoLo cohorts (p=0.02). On multivariable analysis, pre-infusion normal LDH values (HR= 0.41, p<0.001) and comprehensive BRT (HR=0.42, p<0.001) maintained superior PFS. In pts with high preBRT LDH, those who achieved normalization were more likely to have received comprehensive BRT (p=0.002).
Conclusion:

Nearly 40% of pts with elevated pre-apheresis LDH experienced LDH normalization following BRT. These pts have superior clinical outcomes compared to those with persistently elevated LDH and comparable outcomes to those with persistently normal LDH. BRT may neutralize risk factors in at-risk pts with LDH response acting as a potential surrogate for treatment response.

Table 1. Outcomes and toxicity grouped by preBRT and postBRT LDH

		HiHi (%)	HiLo (%)	LoHi (%)	LoLo (%)
All pts		n=66	n=42	n=10	n=39	p
	2yr PFS	16	57	20	52	<0.001
	2yr OS	29	76	13	78	<0.001
	CR to CAR T	34	74	30	77	<0.0001
	CRS Gr 3+	14	5	20	5	0.18
	ICANS Gr 3+	35	12	30	15	0.002
BRT Only		n=35	n=32	n=3	n=19
	2yr PFS	14	63	NA	56	<0.001
	2yr OS	27	79	NA	80	<0.001