Comprehensive Single-Cell Immune Profiling Defines the Patient Multiple Myeloma Microenvironment Following Oncolytic...

Area of Science:

• Oncology
• Immunology
• Virology

Background:

• Preclinical studies indicated that pelareorep (PELA), an oncolytic reovirus formulation, possesses significant immunomodulatory and anti-myeloma properties.
• Multiple myeloma is a hematologic malignancy characterized by uncontrolled proliferation of plasma cells.

Purpose of the Study:

• To evaluate the safety and efficacy of PELA in combination with dexamethasone (Dex) and bortezomib (BZ) in patients with relapsed/refractory multiple myeloma.
• To characterize the changes in the tumor immune microenvironment (TiME) following treatment with PELA/Dex/BZ.

Main Methods:

• A Phase Ib clinical trial enrolled 14 patients with relapsed/refractory multiple myeloma.
• Patients received escalating doses of PELA combined with standard doses of Dex and BZ, with treatment cycles repeated every 28 days.
• Bone marrow and peripheral blood samples were collected pre- and post-treatment for comprehensive immunophenotyping and molecular analyses.

Main Results:

• The PELA/BZ/Dex regimen was well-tolerated, with transient toxicities and no dose-limiting toxicities observed.
• Of 11 response-evaluable patients, 6 (55%) demonstrated a decrease in paraprotein levels.
• Treatment led to increased T-cell and natural killer cell activation, elevated inflammatory cytokine release, and enhanced PD-L1 expression in the bone marrow.

Conclusions:

• PELA/Dex/BZ is a tolerable combination therapy demonstrating anti-myeloma activity in a subset of patients.
• Treatment induced significant immune reprogramming and alterations in the TiME.
• These findings support further investigation of PELA as an immunomodulatory agent for multiple myeloma.