Glucose Regulated Protein (GRP78) as a biomarker of response to bortezomib‐based regimen in multiple myeloma

Abstract

Introduction: GRP78 overexpression has been associated with bortezomib resistance in multiple myeloma (MM) cells. However, serum GRP78 as a maker of bortezomib based treatment response remains unexplored. The objective of the study was to evaluate serum GRP78 levels in MM patients who underwent bortezomib based induction regimen. Methods: After ethical approval, this cross-sectional study was done in adult MM patients who had completed at least 4 cycles of bortezomib based induction therapy. They were classified into responders (complete response (CR), very good partial response (VGPR), partial response (PR)) and non-responders (stable disease (SD) and progressive disease (PD)). Thirty healthy volunteers and twenty newly diagnosed multiple myeloma patients were also recruited to identify the disease associated change in GRP78 levels. Serum GRP78 was estimated by ELISA. Surface and intracellular expression of GRP78 in bone marrow plasma cells was evaluated in a subset of MM patients by flowcytometry. Results: Thirty MM patients who completed at least 4 cycles of bortezomib based induction therapy [median(range): 52 (38–68) years; Male:20] were enrolled. Out of 30 patients, 20 were responders and 10 were non-responders. They were comparable at baseline in all clinical and laboratory parameters except serum M protein which was significantly higher in non-responders (p=0.04). Serum GRP78 levels were not significantly different between responders [median (IQR): 5.2 (3.1,8.0) μg/ml] and non-responders [median (IQR): 4.3 (0.1,7.1) μg/ml] (p=0.356). Although non-significant (p=0.342), median serum GRP78 was higher in newly diagnosed patients when compared to healthy volunteers. Bone marrow plasma cell percentage ranged between 0.2 to 57.8% in the analyzed samples. Intracellular GRP78 expression was found to be higher (1.6 to 5 times) when compared to surface expression in plasma cells as well as in malignant subset of plasma cells. Conclusion: Serum GRP78 did not differ between responders from non-responders in MM patients who underwent bortezomib based induction regimen.