Abstracts Clinical Lymphoma, Myeloma & Leukemia September 2023 S450 treatment, except local radiation in select cases for symptomatic and larger lesions; our patient did not require local radiation. Post therapy, he had very good clinical and radiologic improvement with complete resolution of the parotid gland lesions; PET CT showed mild uptake in the left scapula (SUVmax, 2.6) and the right femoral epicondyle (SUVmax, 2.4). Bony lesions are the most common extramedullary involvement of HCL; glandular involvement is extremely rare. To our knowledge, this is one of the few reported cases of salivary gland involvement by HCL. Further summary of the reported cases will be reviewed at the poster session. Keywords: IBCL, hairy cell leukemia, extramedullary disease, parotid gland, case IBCL-265 Compassionate Use of Plitidepsin in Patients With Non‑Hodgkin Lymphoma (NHL) and SARS‑CoV‑2 Infection Alicia Ortiz Lopez Medicine1, Elena Saiz Lou Medicine2, Raquel Lloris Fernandez Molecular Biology2, Diego Lopez Mendoza Medicine2, Raquel de la Oña Medicine1, Monica Estevez Medicine1, Rebeca Iglesias Medicine1, Patricia Zoilo Medicine3, Carlos Montalban Medicine1, Adolfo de la Fuente Burguera Medicine1 1MD Anderson Cancer Center, Madrid, Spain. 2Virology Unit at PharmaMar, Madrid, Spain. 3Fundación MD Anderson, Madrid, Spain Introduction: Plitidepsin exerts its antitumor and antiviral properties by inhibiting host cell elongation factor-1-alpha (eEF1A) and, thus, the translation of viral proteins (Papapanou M et al., 2021). A clinical trial to evaluate plitidepsin as a treatment for SARS-CoV-2 infection in immunocompromised patients is ongoing (NCT05705167). Objective: To describe the clinical characteristics and evolution of patients diagnosed with NHL admitted for SARS-CoV-2 infection and treated with plitidepsin. Methods: Observational study of NHL patients hospitalized in our center for SARS-CoV-2 between 01/07/2022 and 31/04/2023 and treated with plitidepsin 2.5 mg QD for three days as compassionate use under AEMPS authorization. Results: During the aforementioned period, there were 47 hematological patients admitted for SARSCoV-2 infection. Plitidepsin was administered in 5 patients with NHL who had exhausted other therapeutic options against SARSCoV-2 and presented an unfavorable evolution. Sixty percent (3/5) had received 6 cycles of obitunuzumab and bendamustine (the last dose in patients 1 and 2 were administered < 6 months prior to admission for SARS-CoV-2 and in patient 5, the last dose was administered > 2 years prior to admission). Patients 2 and 5 had received rituximab maintenance, the last dose being administered in both < 2 months prior to admission for SARS-CoV-2. Patient 3 had received 6 cycles of obinutuzumab-COMP and maintenance with obinutuzumab, with the last dose administered 9 months before admission for SARS-COV-2. Patient 4 has a synchronous diagnosis of mantle lymphoma and SARS-CoV-2 infection. Patients were all vaccinated against SARS-CoV-2 and received at least two antiviral treatments prior to plitidepsin. Two patients required admission to the ICU for invasive ventilation, one of which patients died during ICU stay due to SARS-CoV-2 progression. No adverse events related to plitidepsin were observed. After treatment, all patients had negative CRP. Conclusions: Plitidepsin shows a good safety profile in patients with NHL and SARS-CoV-2 infection. Four of the 5 patients presented resolution of SARS-CoV-2 infection. Prospective studies are needed to confirm the effectiveness of plitidepsin as a treatment for SARS-CoV-2 infection in patients with NHL who have received immunochemotherapy. Keywords: IBCL, lymphoma, follicular, plitidepsin, SARS-CoV-2, infection IBCL-270 Signatures of Immune Exhaustion and Suppression in the Tumor Microenvironment of Splenic Marginal Zone Lymphoma Correlate With Inferior Clinical Outcomes Theodora Anagnostou MD1, Zhi-Zhang Yang MD2, Shahrzad Jalali PhD2, Hyo Jin Kim PhD2, Daniel Larson MD2, Xinyi Tang MD, PhD2, Yue Yu PhD2, Joshua Pritchett MD2, Jose Villasboas Bisneto MD2, Tammy Price-Troaka MS2, Patrizia Mondello MD, PhD2, Anne Novak PhD2, Stephen Ansell MD, PhD2 1Icahn School of Medicine at Mount Sinai, New York, USA. 2Mayo Clinic, Rochester, USA Context: The treatment options for indolent B-cell non-Hodgkin lymphoma (NHL) have recently expanded to include T-cell-based therapies, including bispecific antibodies and CART cells. However, these agents, which rely on the fitness of T cells, are currently used at later stages. The composition of T cells in different subtypes of B-NHL and disease stages, which can guide decisions on using these treatment modalities, remains largely unknown. Objective: To comprehensively characterize the composition of intratumoral T cells in splenic marginal zone lymphoma (sMZL) and identify cell subsets predictive of short-term and long-term disease-free intervals. Setting: Retrospectively collected pre-treatment samples from patients treated at Mayo Clinic. Design: We herein use a singlecell immunophenotypic approach based on CyTOF and CITEseq to analyze the T cells from 36 sMZL spleen specimens compared to healthy spleen controls and correlate the levels of different T cell subsets with clinical outcomes. Results: The levels of TFH cells correlated with higher numbers of memory B cells, suggesting involvement of ICOS+ TFH cells in the regulation of lymphoma cell differentiation. TIGIT+ Treg was enriched in sMZL and correlated with the suppression of TH17 and TH22 cells. Intratumoral CD8 were comprised of short-lived, exhausted, and late-stage differentiated cells and thereby functionally impaired. Importantly, these terminally differentiated CD8 levels correlated with inferior event-free survival. In addition, phenotypes of early differentiation (CCR7 expression) correlated with better overall survival (OS), whereas expression of markers of late differentiation (e.g., KLRG1) correlated with inferior OS. Finally, gene expression profiling by CITE-seq demonstrated that exhaustion genes, such as LAG3, KLRG1, PRDM1, and TIGIT, were present on T cells expressing PD1 and TIM3 and more abundant in sMZL. Conclusions: Taken together, our data suggest that immune exhaustion is one of the major
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