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Purpose <p>There has been increased difficulty in developing safe and effective treatment using PI3K inhibitors in heme malignancies, despite the role of PI3K/AKT being well defined in this population. This study was an attempt to conduct exploratory biomarker analysis retrospectively from the phase III CHRONOS-3 trial with the aim to identify a sub-set of patients that could benefit from treatment.</p> Patients and Methods <p>Patients with CD20-positive indolent B-cell lymphoma were randomized 2:1 to receive intravenous copanlisib plus rituximab (C + R) or placebo plus rituximab (P + R). Biomarker analyses were performed to examine potential associations between treatment outcome and phosphatase and tensin homolog (PTEN) protein expression, <i>EZH2</i> and <i>BCL2</i> mutation status via next-generation sequencing, and plasma cytokine levels.</p> Results <p>PTEN presence was associated with significant improvements in progression-free survival (PFS) for C + R over P + R in patients with iNHL (<i>P</i> = 0.001) and FL (<i>P</i> = 0.012). Both the mutant and wild-type <i>EZH2</i> FL patients had equal PFS benefits when treated with copanlisib. A significant improvement in PFS was observed for patients with mutant versus wild-type <i>BCL2</i> FL in the C + R arm (<i>P</i> = 0.002). Overall survival (OS) was significantly improved for patients with iNHL and low or undetectable versus high baseline IL-2 levels in the C + R arm (<i>P</i> &lt; 0.0001, unadjusted).</p> Conclusions <p>PTEN presence, <i>BCL2</i> mutations<i>,</i> and low or undetectable baseline IL-2 levels were associated with improved patient survival following treatment with C + R, supporting a potential role for these biomarkers in guiding treatment selection for patients with indolent non-Hodgkin lymphoma.</p>

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Exploratory biomarker analysis from a phase III study of the PI3K inhibitor, copanlisib, in combination with rituximab in patients with indolent non-Hodgkin lymphoma, a retrospective study

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年2月21日

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  • Shalini Chaturvedi,
  • Anke Weispfenning,
  • Tine Descamps,
  • Sara Bellinvia,
  • David Bauer,
  • Rong Du,
  • Teresa Lunt,
  • Lidia Mongay Soler,
  • Barrett H. Childs,
  • Pier Luigi Zinzani

摘要

Purpose

There has been increased difficulty in developing safe and effective treatment using PI3K inhibitors in heme malignancies, despite the role of PI3K/AKT being well defined in this population. This study was an attempt to conduct exploratory biomarker analysis retrospectively from the phase III CHRONOS-3 trial with the aim to identify a sub-set of patients that could benefit from treatment.

Patients and Methods

Patients with CD20-positive indolent B-cell lymphoma were randomized 2:1 to receive intravenous copanlisib plus rituximab (C + R) or placebo plus rituximab (P + R). Biomarker analyses were performed to examine potential associations between treatment outcome and phosphatase and tensin homolog (PTEN) protein expression, EZH2 and BCL2 mutation status via next-generation sequencing, and plasma cytokine levels.

Results

PTEN presence was associated with significant improvements in progression-free survival (PFS) for C + R over P + R in patients with iNHL (P = 0.001) and FL (P = 0.012). Both the mutant and wild-type EZH2 FL patients had equal PFS benefits when treated with copanlisib. A significant improvement in PFS was observed for patients with mutant versus wild-type BCL2 FL in the C + R arm (P = 0.002). Overall survival (OS) was significantly improved for patients with iNHL and low or undetectable versus high baseline IL-2 levels in the C + R arm (P < 0.0001, unadjusted).

Conclusions

PTEN presence, BCL2 mutations, and low or undetectable baseline IL-2 levels were associated with improved patient survival following treatment with C + R, supporting a potential role for these biomarkers in guiding treatment selection for patients with indolent non-Hodgkin lymphoma.