PB2162 INCIDENCE & SEVERITY OF BORTEZOMIB‐INDUCED PERIPHERAL NEUROPATHY WITH THE USE OF GENERIC BORTEZOMIB IN MONOCLONAL GAMMOPATHIES: A PROSPECTIVE STUDY FROM INDIA

Abstract

Background:The proteasome inhibitor Bortezomib is one of the most effective frontline drugs in the therapeutic armamentarium against monoclonal gammopathies. However, drug‐induced peripheral neuropathy is the major dose‐limiting toxicity and adversely affects quality of life. Generic preparations of bortezomib are mainstay of therapy in resource‐poor countries due to significantly higher cost of original brand of bortezomib.Aims:The present study aims to analyze the incidence & severity of bortezomib‐induced peripheral neuropathy (BIPN) in patients of monoclonal gammopathies receiving generic bortezomib in a resource‐poor setting.MethodsThis non‐randomized, prospective study enrolled total 73 bortezomib‐naïve patients of monoclonal gammopathies between July 2016 & February 2019. Both newly diagnosed & relapsed patients of symptomatic multiple myeloma (MM), Waldenstrom macroglobulinemia (WM) & primary amyloidosis, who had no baseline evidence of peripheral neuropathy were included. Patients having disease‐related neuropathy & patients who had earlier received thalidomide or other neurotoxic drugs were excluded. All study patients received one of the generic bortezomib brands available in India. Bortezomib was initially administered at 1.3 mg/m2 dose, by subcutaneous injection, on days 1,8,15,22 of each 28 days’ cycle. Patients were clinically evaluated for BIPN before each cycle, & at onset of BIPN symptoms. Bortezomib dose was modified according to grade of BIPN (Table 1). Bortezomib was discontinued in grade 3‐4 neuropathy, & restarted after BIPN symptoms improved to < grade 3.Results:Median patient age was 58 years (32‐76 years). Majority (62/73 patients, 85%) had MM, eight patients had WM & three patients had Primary Amyloidosis. Twenty‐seven patients in the study (37%) developed BIPN during treatment. Severity of BIPN in study is shown in Table 2. BIPN symptoms were reversible in 90% patients after discontinuation of bortezomib. Median follow up was 7 months (2‐18 months).imageSummary/Conclusion:In our study, approximately one‐third of patients with monoclonal gammopathies treated with subcutaneously administered generic bortezomib developed bortezomib‐induced peripheral neuropathy. The incidence of severe (grade 3‐4) BIPN was about 12%, leading to temporary/permanent discontinuation of bortezomib and also interfering with quality of life.image