基线免疫营养状态决定 R/R 淋巴瘤中 CAR-T 细胞疗效、生存与安全性：淋巴细胞清除前 PNI 阈值的验证

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.