Evaluation of the Individual Components of the International Metabolic Prognostic Index (IMPI) in the Context of CAR T-Cell Treatment of Lymphoma

CD19 specific chimeric antigen receptor (CAR) T-cell therapy with patient-derived T cells has emerged as novel and effective treatment for relapsed or refractory (r/r) lymphoma. Imaging biomarkers are becoming increasingly important in risk assessment. Recently, the International Prognostic Metabolic Index (IMPI) consisting of metabolic tumor volume (MTV), patient age and Ann Arbor stage was introduced for prognostic assessment in NHL. Since higher patient age is a favorable prognostic factor and a high MTV is a negative prognostic factor in the context of CART, we compared the predictive value of the individual components of the IMPI for progression-free survival (PFS) and overall survival (OS).

Consecutive r/r NHL patients treated with CD19 CAR T-cell therapy and 18F FDG-PET/CT imaging at baseline less than 2 weeks before lymphodepletion and infusion of CAR T cells were included. Patient age was calculated at the time of lymphodepletion. Ann Arbor stages were determined at the baseline PET/CT. MTV was also quantified on the same PET/CT scan before CART and quantified with LIFEx software using semi-automated segmentation with an absolute SUV cutoff of 4 defining metabolic active lymphoma. Survival analysis of PFS and OS was analyzed and plotted with Kaplan-Meier curves.

Out of all examined patients 43 patients were included (37% female, 63% male) with a median age of 66 years and a median baseline MTV of 276 mL. The Ann Arbor stage was I in 4 patients, II in 11 patients, III in 8 patients and IV in 4 patients. The distribution of patients in to two different groups by median IMPI showed minor, non-significant differences in median PFS (97 vs 364 days; p=0.198) and OS (657 days vs not reached; p=0.718). Dichotomization by median MTV alone showed a larger, statistically significant difference (p=0.037) in median PFS (87 vs 659 days) and a larger, non-significant difference in OS (p=0.300). Patients with older age had slightly longer PFS (153 vs 97 days) and a comparable OS (686 vs 657 days), but these findings were not statistically significant (both p>0.05). In addition, there were no relevant differences when the patients were divided into subgroups according to their Ann Arbor stages.

For r/r NHL patients on CART, the IMPI is a promising tool. However, in our study, the MTV alone was superior in estimating prognosis. Future studies with a larger cohort should investigate the best combination of the individual components. The integration of multiple diagnostic modalities as in IMPI offers a promising method to clinically assess patient risk in CART treated lymphoma patients and should be further investigated.

Rejeski:kite/gilead: Consultancy, Honoraria, Other: Travel support, Research Funding; novartis: Honoraria; BMS/celgene: Consultancy, Honoraria; Pierre-Fabre: Other: Travel support. Blumenberg:Kite/GILEAD: Consultancy, Other: congress and travel support, Research Funding; BMS/Celgene: Research Funding; Janssen: Other: congress and travel support, Research Funding, Speakers Bureau; Takeda: Research Funding; Roche: Research Funding, Speakers Bureau; Novartis: Research Funding, Speakers Bureau. Buecklein:BMS: Research Funding; Takeda: Research Funding; Janssen: Research Funding; Pfizer: Consultancy, Honoraria; Pierre Fabre: Consultancy; Otsuka: Consultancy; Amgen: Consultancy, Honoraria; Kite, a Gilead Company: Consultancy, Honoraria, Research Funding; Novartis: Speakers Bureau. Subklewe:Amgen, BMS/Celgene, Gilead/Kite, Janssen, Miltenyi Biotec, Molecular Partners, Novartis, Roche, Seagen, Takeda: Research Funding; 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; AstraZeneca, BMS, Gilead/Kite, GSK, Janssen, LAWG, Novartis, Pfizer, Roche, Springer Healthcare: Speakers Bureau. Kunz:Need, Inc.: Consultancy; mintMedical: Consultancy; Boehringer Ingelheim: Consultancy; Bristol Myers Squibb: Consultancy.