Glofitamab in Combination with Polatuzumab Vedotin Maintains Durable Responses and a Manageable Safety Profile in Patients with Heavily Pre-Treated Relapsed/Refractory (R/R) Large B-Cell Lymphoma (LBCL) Including High-Grade B-Cell Lymphoma (HGBCL): Extended Follow-up of a Phase Ib/II Study

作者：Martin Hutchings, Anna Sureda, Francesc Bosch, Thomas Stauffer Larsen, Paolo Corradini, Abraham Avigdor, María José Terol, Antonio Rueda‐Domínguez, Antonio Pinto, Alan P Skarbnik, Raúl Córdoba, Judit Mészáros Joergensen, Pier Luigi Zinzani, Ronit Gurion, Neta Goldschmidt, Wilfred Leung, Donghang Li, James Relf, Maneesh Tandon, Gila Sellam, Giuseppe Gritti · 发表于：Blood · 年份：2024 · DOI：10.1182/blood-2024-194328 · 被引用次数：14 · 研究领域：CAR-T cell therapy research、Lymphoma Diagnosis and Treatment、Monoclonal and Polyclonal Antibodies Research

Background: TheCD20xCD3 bispecific antibody glofitamab (Glofit) engages and redirects T cells to eliminate B cells. Polatuzumab vedotin (Pola), an antibody-drug conjugate targeting CD79b, has a complementary mechanism of action to Glofit. In this open-label, multicenter, Phase Ib/II study (NCT03533283), Glofit+Pola demonstrated durable responses and manageable safety in patients (pts) with R/R LBCL (Hutchings, et al. ASH 2023). We present updated results with longer follow-up in a greater number of pts with R/R LBCL, including pts with HGBCL and prior chimeric antigen receptor (CAR) T-cell therapy, at the previously confirmed recommended Phase II dose of Glofit (30mg, from Part I of the study) when combined with Pola. Methods: Pts received 1000mg obinutuzumab pre-treatment (Gpt) on Cycle (C)1 Day (D)1, 7 days prior to the first Glofit dose to mitigate risk of cytokine release syndrome (CRS). Pola 1.8mg/kg was given on C1D2 and D1 of C2-6 (21-day cycles), and Glofit as step-up dosing in C1 (D8, 2.5mg; D15, 10mg) followed by the target dose (30mg) on D1 of C2-12 (21-day cycles). Fixed treatment of 6 cycles of Pola and 12 cycles of Glofit were administered, unless pts discontinued treatment due to disease progression, unacceptable toxicities, or withdrawal of consent. Results: At the clinical cutoff date (CCOD; Feb 16, 2024), 129 pts had received ≥1 dose of study treatment (DLBCL, n=57; HGBCL, n=44; transformed follicular lymphoma [trFL], n=26; primary mediastinal LBCL [PMBCL], ...