Characterization of Hemophagocytic Lymphohistio(HLH）in Relapsed Diffuse Large B-Cell Lymphoma Patients after CAR-T Therapy

Abstract

Background: Patients with chemotherapy-refractory diffuse large B-cell lymphoma (DLBCL) have poor prognoses. The objective response rate of patients with standard salvage regimens is 26%, while CART therapy have complete remission (CR) rates of 40%- 54% against DLBCL. Half of DLBCL patients relapsed or progressed after chimeric CAR-T cell therapy, but only a few of them were accompanied by HLH. Its clinical characteristics are unclear. This study aimed to investigate the clinical characteristics of these patients. Methods: We retrospectively analyzed the clinical data of 8 patients with relapsed DLBCL lymphoma accompany by HLH after CAR-T therapy between May 2019 and July 2023(NCT02537977 and NCT04036019). We investigate the clinical characteristics of these patients, compare the survival between patients with and without CR after CAR-T therapy, compare the survival between patients with and without CRS after CAR-T therapy. Results: 8 R/R DLBCL patients were enrolled. Median age was 59.5 years (range, 37-69), and 6(75%) patients had non-germinal center B-cell-like (non-GCB) DLBCL, one had GCB DLBCL, one had transformed DLBCL. 2 patients (25.0%) had HLH before CAR-T treatment previously. Among them, 3 patients (37.5%) achieved CR after CART therapy, while 3 patients (37.5%) achieved partial remission. ALL of the patients (100%) relapsed or progressed, and all of them died because of disease progression. With a median follow-up of 7 months, the median overall survival (OS) was 206.0 days (95%CI 106.2-305.8) and progress-free survival (PFS) was 125.0 days (95%CI 40.5-210.0). Particularly，the median time from HLH to death was only 45.0 days (95%CI: 22.8-67.2). 6 patients (75.0%) occurred grade 1-2 CRS, no patient occurred ≥grade 3 CRS, and 2 patients (25.0%) did not occurred any CRS. The median OS was 328.0 days and 142.0 days (95%CI 60.4-223.6) for patients without CRS and with CRS1-2, respectively. There is significantly different in OS for patients with and without CRS ( P=0.03). The median OS was 328.0 days (95%CI 217.6-438.4) and 142.0 days (95%CI 133.4-150.6) for patients with CR and without CR, respectively. The median PFS was 257.0 days (95%CI 103.4-410.6) and 77.0 days (95%CI 8.3-145.7) for patients with CR and without CR. There is significantly different in OS and PFS for patients with CR and other patients ( P=0.01 and P=0.01). Conclusion: Hemophagocytic lymphohistiocytosis (HLH) is a rare and life threatening disorder. The prognosis of patients with relapsed DLBCL lymphoma accompany by HLH after CAR-T therapy is very poor. Patients with CRS during CART therapy may more likely have HLH when DLBCL relapse. The patients without CRS have better survival time than those with CRS during CART therapy. We hypothesis that because both HLH and CRS is inflammatory syndrome resulting from T-cell activation.