Combination of Glofitamab with Pirtobrutinib in BTK Inhibitor (BTKi)-Naive or Btki-Intolerant Patients with Relapsed or Refractory (R/R) Mantle Cell Lymphoma (MCL): A Multicenter Phase 2 Study of the University of California Hematologic Malignancies Consortium

作者：Madhav Seshadri, Chiung‐Yu Huang, Hildy Donner, William Pearse, Patricia A. Young, Monica Mead, Naseem Esteghamat, Christine Thacker, Lauren Nguyen, Weiyun Z. Ai, Michael A. Spinner, Lawrence D. Kaplan, Charalambos Andreadis · 发表于：Blood · 年份：2024 · DOI：10.1182/blood-2024-209493 · 被引用次数：1 · 研究领域：Chronic Lymphocytic Leukemia Research、Lymphoma Diagnosis and Treatment、Viral-associated cancers and disorders

Background MCL is an aggressive and incurable B-cell malignancy. Pirtobrutinib is a noncovalent BTKi with single-agent activity in patients with R/R MCL (Mato 2021). Bispecific antibodies, which recruit native T-cells to induce cancer-directed immune responses, represent an emerging treatment modality in this disease. Data from a phase 1/2 trial of glofitamab, a CD20xCD3 bispecific antibody with a novel 2:1 format, in patients with R/R MCL showed overall response rate 85% and complete response rate 78.3% (Phillips 2024). MCL can have an immune evasive phenotype, which is associated with inferior prognosis and may contribute to resistance to immunotherapies. Importantly, there is evidence that BTK inhibition may reverse these phenotypes through lymphoma-intrinsic and -extrinsic mechanisms, such as modulating immune checkpoint ligand expression, cytokine expression profiles, and cell composition of the microenvironment (Li 2018, Papin 2019). Based on (1) single-agent activity of both glofitamab and pirtobrutinib in R/R MCL, (2) preclinical data demonstrating that BTK inhibition has immunomodulatory effects which may potentiate anti-lymphoma immune responses, and (3) largely non-overlapping toxicities, this investigator-initiated trial (NCT06252675) was designed to test the hypothesis that the combination of pirtobrutinib with glofitamab will be highly effective with tolerable toxicity in BTKi-naive or BTKi-intolerant patients with R/R MCL. Objectives The primary objectives of t...