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Suppl Fig 2 from Targeting the Inducible T-cell Costimulator (ICOS) in Patients with Relapsed/Refractory T-follicular Helper Phenotype Peripheral T-cell and Angioimmunoblastic T-cell Lymphoma

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posted on 2023-04-04, 14:04 authored by Julio C. Chavez, Francine M. Foss, Basem M. William, Jonathan E. Brammer, Sonali M. Smith, Anca Prica, Jasmine M. Zain, Joseph M. Tuscano, Harsh Shah, Neha Mehta-Shah, Praveen Ramakrishnan Geethakumari, Ben X. Wang, Stephanie Zantinge, Lisa Wang, Ling Zhang, Anmarie Boutrin, Weiguang Zhao, Lily Cheng, Nathan Standifer, Lisa Hewitt, Enowmpey Enowtambong, Weiping Shao, Shringi Sharma, Gianluca Carlesso, Jeffrey A. Moscow, Lillian L. Siu

Supplemental Figure 2. MEDI-570 effects on lymphocyte and leukocyte populations. Baseline-normalized, absolute counts (ABS) of circulating cell populations were plotted on study days 1, 7, 14 and 21 from patients enrolled in each dose group as indicated. A) Total CD3+CD8+ cytotoxic T cells B) CD14+ monocytes C) CD3-CD56+ and/or CD16+ NK cells D) CD3-CD19+ B cells.

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ARTICLE ABSTRACT

Proliferation of T-follicular helper (TFH) CD4+ T cells is a postulated pathogenic mechanism for T-cell non-Hodgkin lymphomas (T-NHL). The inducible T-cell costimulator (ICOS) is highly expressed by TFH, representing a potential target. MEDI-570 is a monoclonal antibody against ICOS, which eliminates ICOS+ cells in preclinical models. We report the safety, pharmacokinetics (PK), pharmacodynamics (PD), and clinical activity of MEDI-570 in T-NHL. NCI-9930 is a phase I, first-in-human study of MEDI-570 in relapsed/refractory malignant T-NHL known to express ICOS. MEDI-570 was administered intravenously every 3 weeks for up to 12 cycles. Primary endpoints were safety, dose-limiting toxicities (DLT), and recommended phase II dose (RP2D). Secondary and exploratory endpoints included efficacy parameters and various correlative studies. This study is supported by the National Cancer Institute (NCT02520791). Twenty-three patients were enrolled and received MEDI-570 at five dose levels (0.01–3 mg/kg). Sixteen (70%) had angioimmunoblastic T-cell lymphoma (AITL); median age was 67 years (29–86) and the median prior lines of therapies was 3 (1–16). Most common grade 3 or 4 adverse events were decreased CD4+ T cells (57%), lymphopenia (22%), anemia (13%), and infusion-related reactions (9%). No DLTs were observed. The RP2D was determined at 3 mg/kg. Analysis of T-cell subsets showed reductions in CD4+ICOS+ T cells reflecting its effects on TFH cells. The response rate in AITL was 44%. MEDI-570 was well tolerated and showed promising clinical activity in refractory AITL. MEDI-570 resulted in sustained reduction of ICOS+ T lymphocytes.

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