Abstracts Clinical Lymphoma, Myeloma & Leukemia September 2023 S422 ABCL-175 Relevance of Allele Imbalance in 9p24.1 and 16p13.13 STR Loci to PDL1 and HLA‑DR Expression in Primary Mediastinal B‑Cell Lymphoma (PMBCL) Runiza Abdurashidova MD, Natalya Risinskaya MD, PhD, Yana Mangasarova MD, PhD, Elena Nikulina MD, Anna Yushkova MD, Irina Shupletsova MD, PhD, Alla Kovrigina MD, PhD, Vadim Surin MD, Hunan Julhakyan MD, PhD, Andrey Sudarikov MD, PhD National Medical Research Center for Hematology, Moscow, Russian Federation Context: PMBCL is an NHL variant that responds to immune checkpoint inhibitors (ICIs) therapy in approximately half of the cases. Molecular factors predicting possible responses to immunotherapy for PMBCL are not yet described. Evaluation of programmed cell death ligand-1/ligand-2 (PD-L1/L2) expression level in tumor samples has proven clinical utility for ICI response prediction in various solid tumors. HLA-DR overexpression may be another marker associated with response to anti-PD-1/PD-L1 therapy. MHCII gene expression is associated with the transcription of the gene encoding the CIITA trans-activator, a crucial MHCII gene regulatory factor. The PD-L1 and CIITA gene expression level could be affected by copy number variations associated with 9p24.1 and 16p13.13 chromosomal lesions (losses or gains). Analysis of appropriate short tandem repeat (STR) markers is a straightforward way to detect these lesions. Objective: To analyze the possible association of STR allele imbalance (AI) in 9p24.1 with PD-L1 expression level and STR AI in 16p13.13 with HLA-DR expression level in tumor cells of PMBCL patients. Design: STR-loci at 9p24.1 and 16p13.13 of the paired tumor/control DNA samples were analyzed in a cohort of 27 PMBCL patients admitted to the National Medical Research Center for Hematology (2013-2020). STR data was compared with the expression of PD-L1 and HLA-DR, respectively. An immunohistochemical study of PD-L1, HLA-DR, and tumor DNA extraction was performed on mediastinal biopsy samples from archival paraffin blocks. Patients: De novo-diagnosed PMBCL patients were included, while pretreated patients were excluded. Results: AI in the 9p24.1 was found in 14 of 27 patients (52%). PDL1 expression was found in 10 (6 with AI 9p24.1) of 27 patients (37%). AI in16p13.13 was found in 8 of 27 patients (30%). HLA-DR expression was observed in 20 (6 with AI 16p13.13) of 27(74%) patients with PMBCL. However, a significant correlation between STR aberrations and the expression of related genes has not been found (chi-square statistic, P>0.05). Conclusions: STR AI in 9p24.1 and 16p13.13 and PD-L1 and HLA-DR expression are highly frequent though probably independent events relevant to immunotherapy response in PMBCL. Funding: This study was supported by Rakfond grant 2/2020. Keywords: ABCL, primary mediastinal B-cell lymphoma, STR, PDL1, HLA-DR expression ABCL-176 New Strategy of First‑Line Treatment of Primary Mediastinal Lymphoma (PML): One Center Experience Nelly Gabeeva MD, PhD, Svetlana Tatarnikova MD, Darya Koroleva MD, PhD, Anna Smolyaninova MD, PhD, Valeria Kimaykina MD, Svetlana Smirnova MD, PhD, Elena Nikulina MD, Eduard Gemdzhyan MD, Hunan Julhakyan MD, PhD, Andrey Sudarikov MD, PhD, Eugenie Zvonkov MD, PhD National Research Center for Hematology, Moscow, Russian Federation Introduction: PML is an aggressive lymphoid tumor with a unique biology. Regardless of the first-line therapy, refractory disease can occur in up to 10% of patients and correlates with poor outcomes. The long-term toxicity of radiotherapy and the risk of recurrence with central nervous system (CNS) involvement are subjects of ongoing debate. More intensive regimens are associated with significant toxicity. We developed a hybrid protocol for the first-line treatment of PML. To improve the outcome, we integrated lenalidomide as an inhibitor of the NF-kB pathway. Aim: To assess the efficacy of twostep pilot prospective protocols PML-16 and PML-19 for untreated PML. Materials and Methods: From January 2016 to June 2022, 34 previously untreated PML patients were included (median age 32, stage >I - 60%, extramediastinal lesions -14%, bulky disease -73%). PET-CT and ctDNA were performed before CT, after 2 cycles, and after the end of CT. Results: Our first step (PML-16 protocol) was intensifying the induction phase. Eighteen patients received treatment according to this protocol, consisting of 6 cycles: (i) induction (blocks A and B of R-mNHL-BFM-90); (ii) consolidation (4 cycles of R-EPOCH). The program was interrupted after 2-5 cycles due to prolonged cytopenia in 5/18 patients. After the end of therapy, all 18 patients achieved PET-negative remission. Given the efficacy of this approach, we developed the next step consisting of 4 cycles (PML-19): (i) induction (A and B of R-mNHL-BFM-90); (ii) consolidation with 2 courses of R-EPOCH; (iii) lenalidomide 1-10 days of each course. Sixteen patients received treatment according to the PML-19. After the end of therapy, 9 (56%) patients were PET-negative; 7 (44%) were PET-positive (D4–5 score). ctDNA was performed in 15 patients. Regardless of the PET-CT status, ctDNA was eliminated in all patients after the end of therapy. During follow-up, the PET-CT metabolic activity decreased to physiological without consolidating therapy. With a median follow-up of 36 months (9-76 months), all 34 patients are in complete remission. Conclusion: Our preliminary results indicate that the new approach had a high cure rate in PML patients. ctDNA is a reliable marker for response assessment in PML. Keywords: AML, primary mediastinal lymphoma, ctDNA, lenalidomide, NF-kB
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