Clinical outcome and exploratory analysis of endoplasmic reticulum stress marker in feline plasma cell-derived neoplasms treated with bortezomib: a retrospective pilot study

Feline plasma cell-derived neoplasms, including extramedullary plasmacytoma and multiple myeloma, are rare and frequently associated with poor prognosis. Bortezomib, a proteasome inhibitor used to treat human multiple myeloma, has shown antitumor activity in canine and feline neoplastic cells. However, the clinical data on cats remain limited. This study retrospectively evaluated the clinical outcomes of cats with plasma cell-derived neoplasia treated with bortezomib, and explored the potential association between treatment response and endoplasmic reticulum stress-related marker expression. Medical records from two referral centers were reviewed to identify cats diagnosed with plasma cell-derived neoplasms that received at least one dose of bortezomib between April 2022 and December 2025. Treatment response was assessed using the Veterinary Cooperative Oncology Group (VCOG) response evaluation criteria for solid tumors in dogs v1 and by measuring changes in M protein production. Adverse events were graded according to the VCOG Common Terminology Criteria for Adverse Events v2. Immunohistochemistry for activating transcription factor 6 was performed in representative responder and non-responder cases, and nuclear diaminobenzidine intensity was semi-quantified using the QuPath software. Five cats met the inclusion criteria. Objective responses were observed in four cases, including two cases each of complete and partial remission. The progression-free interval ranged from 10 to > 811 days. All responding patients exhibited M protein production, whereas non-responding patients did not. Bortezomib is generally well tolerated, with transient neutropenia and peripheral neuropathy being the most notable adverse events reported. Semiquantitative analysis of immunostaining for activating transcription factor 6 demonstrated higher nuclear expression intensity in complete responders than in non-responders. This retrospective pilot case-series suggests that bortezomib exhibits therapeutic activity against feline plasma cell-derived neoplasms. Exploratory analysis of nuclear activating transcription factor 6 expression may support further investigation of endoplasmic reticulum stress–related biomarkers as potential predictors of proteasome inhibitor sensitivity in cats and warrant prospective biomarker-based studies.