Abstracts Clinical Lymphoma, Myeloma & Leukemia September 2023 S414 AHOD1331, and BREACH trials, the magnitude of benefit with Bv treatment in terms of either PFS or OS was significantly higher in both PET2-negative and PET2-positive patients. Additionally, the ongoing ACCRU-LY study incorporating nivolumab and Bv into frontline treatment reports a 97% rate of interim PET negativity with a 100% 2-year PFS. The review of LLUCC patients showed that among the 40 patients who received BvAVD, 24 patients were PET2-negative and 12 patients PET2-positive. All the PET2-negative patients had a negative EOT-PET indicating no progression in cancer. Four out of 12 PET2-positive patients had a positive EOT-PET. The results of PET2 scans did not have any meaningful impact on management of patients as only 1 patient had a change in chemotherapy regimen after PET2 among all 40 patients who initially started on BvAVD. There were no differences between the outcomes of PET2-positive patients who had negative EOT-PET compared to PET2-negative patients as all the 24 patients with negative PET2 as well as all the 8 patients with positive PET2 and negative EOT-PET remained in complete remission at the end of treatment. Conclusion: Incorporation of brentuximab into frontline treatment results in superior efficacy regardless of PET2 results. Our data along with previous studies point to the loss of predictive value and therefore redundancy of an interim PET2 scan, providing evidence for safe omission of PET2 in treatment regimens containing Bv. Keywords: HL, brentuximab vedotin, Hodgkin lymphoma, PET2, EOT-PET, AAVD Aggressive B-Cell Lymphoma ABCL-004 Salvage Radiotherapy in Relapsed/ Refractory Large B‑Cell Lymphoma After CAR T‑Cell Therapy Failure Hazim Ababneh MD1, Andrea Ng MD, MPH2, Matthew Frigault MD1, Jeremy Abramson MD1, Patrick Johnson MD1, Caron Jacobson MD3, Chirayu Patel MD, MPH1 1Massachusetts General Hospital/Harvard Medical School, Boston, USA. 2Brigham and Women’s Hospital, Boston, USA. 3Dana-Farber Cancer Institute, Boston, USA Introduction: We sought to describe our experience with salvage radiation therapy (RT) relative to other therapies in patients with relapsed/refractory large B-cell lymphoma (LBCL) post-CD19targeted chimeric antigen receptor (CAR T)-cell therapy failure. Methods: We conducted a multi-institutional retrospective study of patients who relapsed following CAR T-cell therapy (axicabtagene ciloleucel [axi-cel] or tisagenlecleucel [tisa-cel]) and received salvage therapies (RT alone, systemic therapy alone, or combined modality therapy [CMT]). Results: A total of 120 patients with post-CAR T relapsed with LBCL received salvage therapies (RT alone, 14 patients; CMT, 40 patients; systemic therapy alone, 66 patients). The median follow-up after CAR T-cell infusion was 10.2 months (interquartile range [IQR]: 5.2-20.9 months). Failure occurred in previously involved sites prior to CAR T-cell therapy in 78% of patients (n=93). The median time from CAR T-cell therapy infusion to the start of salvage therapy was 3.4 months (IQR: 1.7-6.5 months). A total of 93 sites were irradiated among the 54 patients who received RT in the RT and CMT cohorts. The median dose/fractionations were 30 Gy (range, 4-50.4 Gy) and 10 fractions (range, 1-28 fractions). The 1-year local control (LC) rate for the 81 assessable sites was 84%. The median OS from the start date of RT was significantly higher among patients who received comprehensive RT vs focal RT (19.1 months vs 3.0 months, P≤.001); 26 of the 29 patients who received comprehensive RT had only a single site of disease, but survival for the 3 patients with >1 site of disease was not statistically different (P=0.17). On multivariate survival analysis, achieving PR or CR post-CAR T (HR=0.5, 95% CI: 0.3-0.9, P=0.01) was independently associated with superior OS. Conclusion: RT provides excellent local control for LBCL relapsed post-CAR-T cell therapy. Patients with limited disease burden who were treated with comprehensive RT had favorable OS relative to patients with more extensive disease who received focal RT. Future prospective studies should investigate combining RT with other novel strategies, including lenalidomide, polatuzumab vedotin, loncastuximab tesirine, bispecific antibodies, and/or consolidation with allogeneic HSCT to optimize patient outcomes. Keywords: CAR T-cell therapy, ABCL, LBCL, radiation therapy ABCL-012 Therapeutic Potential of Niclosamide in Suppressing Immune Escape During the Progression of Diffuse Large B‑Cell Lymphoma Carcinogenesis Chun-Yu Chuang PhD1, Yin-Kai Chen MD2, Chen-Yan Li MS1 1Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu, Taiwan. 2Department of Hematology, National Taiwan University Cancer Center, Taipei, Taiwan Context: Diffuse large B-cell lymphoma (DLBCL) is a common type of non-Hodgkin lymphoma (NHL) with an increasing incidence in recent years. Immune escape is an important characteristic of cancer development and metastasis. Niclosamide (NIC) is an oral antiparasitic drug that has been found to block immune checkpoints and believed to have potential in cancer treatment. Objective: This study aims to investigate whether NIC therapy can mediate DLBCL carcinogenesis by regulating immune escape. Methods: Activated B-cell-like (ABC) DLBCL presents lower sensitivity to chemotherapy and poorer prognosis. SU-DHL-2 (ABC-like DLBCL) cell line was used for validation. Results: In SU-DHL-2 cells, NIC treatment caused a time- and dose-dependent decrease in the survival rate and reduced MYC expression, leading to G0/ G1 cell cycle arrest and reduced cell proliferation. Additionally, NIC downregulated PIK3CB, AKT1, and PD-L1, and increased ATF4, HSPA5, and PTEN expression. When SU-DHL-2 cells were co-cultured with NK-92 cells, NIC also decreased PD-1 and PDL1 expression. Conclusions: This study found that NIC inhibits immune escape in SU-DHL-2 cells and induces cell apoptosis by regulating PD-L1 expression, leading to reduced cell proliferation.
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