Baseline immunonutritional status drives CAR T-cell efficacy, survival, and safety in R/R lymphoma: validation of a pre-lymphodepletion PNI threshold

Abstract

Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment landscape for relapsed/refractory (R/R) lymphoma. However, heterogeneous responses and treatment-related toxicities remain significant challenges. The prognostic nutritional index (PNI), reflecting both nutritional status and systemic immune competence, has emerged as a potential biomarker in various malignancies. This study aimed to evaluate the predictive value of the PNI assessed specifically prior to lymphodepletion in patients with R/R lymphoma receiving CAR T-cell therapy. We retrospectively analyzed 449 patients with R/R lymphoma treated with CAR T cells. The PNI was calculated using serum albumin levels and absolute lymphocyte counts measured before administering lymphodepleting chemotherapy. The optimal PNI cutoff for predicting survival was determined to be 39.2 using maximally selected rank statistics. The patients were stratified into high-PNI (> 39.2, n = 363) and low-PNI (≤ 39.2, n = 86) groups on the basis of the PNI cutoff value. The median age of the patients was 52 years. All patients had R/R aggressive B-cell lymphoma and were treated with CAR T cells. Compared with patients in the low-PNI group, patients in the high-PNI group achieved significantly superior clinical responses, with higher overall response rates (ORRs: 65.5% vs. 44.2%, P < 0.001) and complete response rates (CRRs: 52.2% vs. 27.9%, P < 0.001). The median follow-up period was 33.12 months, and long-term survival markedly improved among patients in the high-PNI group; the 5-year overall survival (OS) rates were 59.02% vs. 21.88% (P < 0.001), and the 5-year progression-free survival (PFS) rates were 42.69% vs. 13.29% (P < 0.001) for patients in the high- and low-PNI groups, respectively. In terms of safety, multivariate analysis confirmed that a high PNI independently reduced the risk of any-grade CRS (P = 0.047), but was not significantly associated with grade ≥ 3 CRS (P = 0.121). No significant association was observed between a high PNI and the occurrence or severity of ICANS (all P > 0.05). Multivariate analysis revealed that a PNI > 39.2 remained an independent predictor of both OS (HR = 0.425, P < 0.001) and PFS (HR = 0.542, P < 0.001). The pre-lymphodepletion PNI is a simple, noninvasive, and robust tool for predicting therapeutic efficacy, long-term survival, and treatment-related toxicity in patients with R/R lymphoma receiving CAR T-cell therapy. A PNI threshold of 39.2 provides a valuable reference for risk stratification and clinical management.