Enitociclib ( VIP152 ), venetoclax and prednisone in relapsed or refractory aggressive non‐Hodgkin lymphoma

作者：Max J. Gordon, Rahul Lakhotia, Stefania Pittaluga, Svetlana Pack, Anna Marie Juanitez, Ahmed Hamdy, Amy J. Johnson, Melanie M. Frigault, Raquel Izumi, Mark Raffeld, Mark Roschewski, Wyndham H. Wilson, Christopher Melani · 发表于：British Journal of Haematology · 年份：2025 · DOI：10.1111/bjh.70234 · 被引用次数：1 · 研究领域：Lymphoma Diagnosis and Treatment、Cancer-related Molecular Pathways、Protein Degradation and Inhibitors

To the Editor, Dysregulated proliferation and survival are fundamental hallmarks of cancer. In aggressive lymphomas, alterations in the MYC oncogene and anti-apoptotic regulators such as MCL1 and BCL2 are frequent promoters of this phenotype.1-3 MYC is essential for cell growth and proliferation whereas BCL2 and MCL1 regulate cell death and are potentially important therapeutic targets.4 Unfortunately, directly targeting MYC or MCL1 has been challenging due to poor clinical activity and excess toxicity.5, 6 While the BCL2 inhibitor venetoclax has shown modest single-agent activity in aggressive lymphomas, including diffuse large B-cell lymphoma (DLBCL) and peripheral T-cell lymphoma (PTCL), durable remissions are rarely observed.7, 8 Cyclin-dependent kinase 9 (CDK9) regulates the activity of RNA polymerase II (RNAPII) and CDK9 inhibition has been identified as a mechanism to indirectly target MYC and MCL1, among other short-lived proteins, through inhibition of RNAPII transcription.9, 10 CDK9 inhibitors have shown activity in relapsed or refractory (R/R) lymphomas; however, durable remissions are observed in a minority of patients. In a study of single-agent enitociclib (VIP152), a CDK9 inhibitor, two of seven patients with high-grade B-cell lymphoma double-hit with MYC and BCL2 rearrangements (HGBCL-DH-BCL2) achieved complete response (CR), both ongoing after 2.3 and 3.7 years of follow-up.11, 12 Increased BCL2 and MCL1 have been identified as mechanisms of resistance to CDK...