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Aim: To establish the role of inflammation in bortezomib induced peripheral neuropathy (BIPN). Background: Peripheral neuropathy is the dose-limiting toxicity of bortezomib which can lead to discontinuation of the treatment. There are multiple mechanisms involved in the disposition of BIPN. However, the role of inflammatory mediators is still under investigation. The complete understanding of inflammatory markers in relation to BIPN can lead to the development of effective therapy for prophylaxis and treatment of peripheral neuropathy. Objective: Based on the available data, postulate the role of inflammatory mediators in the development of peripheral neuropathy due to bortezomib. Method: The “Pubmed” and “Google Scholar” were used as the search engines with terms like “peripheral neuropathy”, “bortezomib induced peripheral neuropathy” and “inflammation”. Original research, case reports and review articles were considered. Results: Bortezomib use is associated with the development of peripheral neuropathy. This effect is due to the damage to Schwann cells and dorsal root ganglion neurons; mitochondrial damage; increased ion channel susceptibility; and higher infiltration of macrophages in the spinal cord. All these factors collectively increase the secretion of inflammatory mediators and lead to the development of neuropathic pain. Conclusion: Targeting inflammatory mediators may be helpful in the treatment of bortezomib-induced peripheral neuropathy.

GRP78 overexpression in myeloma cells has been associated with bortezomib resistance in multiple myeloma (MM). 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 a bortezomib-based induction regimen. This cross-sectional study included adult MM patients (n=30) who completed at least four cycles of bortezomib-based induction therapy. Healthy volunteers (n=30) and newly diagnosed MM patients (n=19) were also recruited to identify the diseaseassociated change in GRP78 levels. Serum GRP78 was estimated by ELISA. Surface and intracellular expression of GRP78 in bone marrow plasma cells was evaluated in ten MM patients by flow cytometry. Among 30 MM patients [median (range): 52 (38-68) years; 20 males] who completed at least four cycles of bortezomib-based induction therapy, 20 were responders and 10 were non-responders. 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=0.4). Although non-significant (p=0.3), median serum GRP78 was higher in newly diagnosed patients when compared to healthy volunteers. Bone marrow plasma cells ranged from 0.2 to 57.8% in the analyzed samples. Intracellular GRP78 expression in bone marrow plasma cells was higher (1.6 to 5 times) when compared to surface expression. To conclude, serum GRP78 levels vary widely in different MM patient groups but did not correlate with response to a bortezomib-based induction regimen.

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