Predictive Value of Maximum Tumor Dissemination (Dmax) in Lymphoma Patients Treated with CD19 Specific CAR T-Cell Therapy

CD19 specific chimeric antigen receptor T-cell therapy (CART) has emerged as an effective treatment for relapsed or refractory (r/r) lymphoma. Imaging biomarkers are becoming increasingly important in risk assessment. The maximum distance (Dmax) of lymphoma lesions across the body holds potential as prognostic imaging biomarker in lymphoma treated with conventional therapies but has not been studied in context of CART. We evaluated Dmax at baseline imaging as a prognostic tool for assessment of metabolic and overall response, progression-free survival (PFS) and overall survival (OS).

Consecutive r/r lymphoma patients with PET/CT or CT imaging at baseline (BL) and PET/CT at 3 months follow-up (FU) after CAR T-cell transfusion were included. Dmax was measured in cm at BL. Patients were divided into three equal risk groups according to Dmax: low, intermediate, and high. Ann Arbor stages were calculated as baseline for comparison. The sum of product diameters (SPD) in mm² of up to 6 target lesions was used to represent tumor burden (TB). Overall response according to Lugano criteria and the Deauville score were determined in FU PET/CT imaging.

Of 103 patients with baseline imaging and measurable Dmax, 63 had a PET/CT after 3 months. Median Dmax was 40.0 cm (IQR: 16.4 - 70.3 cm) at BL. TB decreased in the median from BL with 4,095 mm² to 770 mm² at FU imaging. Median TB was significantly higher in the intermediate and high-risk group compared to the low-risk group (p=0.005) with 7,222 mm² (IQR: 3,355 - 11,941 mm²), 4,649 mm² (IQR: 2,376 - 10,406 mm²) and 1,739 mm² (IQR: 715 - 7,402 mm²), respectively. Intermediate and high-risk groups showed significantly higher Ann Arbor stages (p<0.001). The survival analysis revealed a significantly (p=0.030) shorter PFS in the high-risk group compared to the other patients (91 vs 364 days), but no relevant differences in OS (p=0.151), which is comparable to the analysis by grouping according to Ann Arbor stage. In addition, no significant differences in Deauville score and ORR were detected.

Patients with high Dmax showed a shorter PFS, but no significant differences in OS. In addition, there was no superiority over the Ann Arbor stages for risk assessment. Nevertheless, Dmax as an interval-scaled parameter represents a useful alternative to the latter. Dmax in the context of CART as an interval-scaled parameter could be used in multiparametric scores to guide and improve patient care.

Kunz:Bristol Myers Squibb: Consultancy; Boehringer Ingelheim: Consultancy; mintMedical: Consultancy; Need, Inc.: Consultancy. Blumenberg:BMS/Celgene: Research Funding; Kite/GILEAD: Consultancy, Other: congress and travel support, Research Funding; Janssen: Other: congress and travel support, Research Funding, Speakers Bureau; Novartis: Research Funding, Speakers Bureau; Roche: Research Funding, Speakers Bureau; Takeda: Research Funding. Rejeski:Kite/Gilead: Consultancy, Honoraria, Other: Travel Support, Research Funding; Novartis: Honoraria; BMS/CELGENE: Consultancy, Honoraria; Pierre-Fabre: Other: Travel Support. Subklewe:AstraZeneca, BMS, Gilead/Kite, GSK, Janssen, LAWG, Novartis, Pfizer, Roche, Springer Healthcare: Speakers Bureau; AbbVie, Amgen, Autolus, AvenCell, BMS, CanCell Therapeutics, Genmab US, Gilead, Ichnos Sciences, Incyte Biosciences, Interius BioTherapeutics, Janssen, Miltenyi Biomedicine, Molecular Partners, Nektar Therapeutics, Novartis, Orbital Therapeutics, Pfizer,: Honoraria; Amgen, BMS/Celgene, Gilead/Kite, Janssen, Miltenyi Biotec, Molecular Partners, Novartis, Roche, Seagen, Takeda: Research Funding.