Impact of Body Mass Index (BMI) on the Incidence of Bortezomib -Induced Peripheral Neuropathy (BIPN) in Patients with Newly Diagnosed Multiple Myeloma (MM)

Background

Peripheral neuropathy (PN) is one of the most common dose-limiting toxicities associated with bortezomib (B); it can lead to dose reductions or therapy discontinuation. Diabetes mellitus, prior thalidomide treatment, and advanced age have been identified as being risk factors for the developing bortezomib-induced peripheral neuropathy (BIPN). Obesity has been identified as being a risk factor for the development of PN with other neurotoxic anticancer agents.We aimed to evaluate the impact of BMI on the incidence and severity of BIPN.

Methods

This is a retrospective, single-center study of patients treated at Levine Cancer Institute with subcutaneous B between January 1, 2012 and June 1, 2017. Eligible patients received at least one full cycle of subcutaneous B and had previously untreated, newly diagnosed MM. Patients who received intravenous B or concomitant thalidomide were excluded. Patients were divided into three groups based on their BMI: normal/underweight (BMI <25), overweight (BMI 25-29.9), and obese (BMI ≥ 30). Patient and disease characteristics were summarized with frequencies and proportions for categorical factors and descriptive statistics for continuous factors. The individual impact of BMI on PN incidence was evaluated with univariable logistic regression. Multivariable logistic regression evaluated additional factors that might be confounders: gender, race, age, MM type and stage, smoking status, comorbidities, concomitant antimyeloma therapy, and B dose and schedule. We used the Common Toxicity Criteria for Adverse Events (CTCAE v4.03) to grade the intensity of the neurologic symptoms. Association of grade of PN with BMI was evaluated with Fisher's exact test.

Results

A total of 143 patients fit the inclusion criteria were identified (59% were male, and 41% were female, median age was 66 years (range 25-85). Patients across the three groups received B at similar doses and schedules (weekly vs. biweekly). Obese patients had an increased incidence in developing BIPN (56.4%) compared to normal/underweight (17.3%) and overweight patients (26.9%). On multivariable analysis adjusting for B dose and schedule, obesity was associated with increased odds in developing BIPN compared to normal/underweight patients (OR 7.24, 95% CI 2.37-22.13; p=0.002). Further analysis showed that compared to normal/underweight and overweight patients, obesity was not found to associated with an increased risk of grade 3-4 BIPN (p=0.451). Obese patients receiving B required dose adjustments (31%) and started medications (36%) for BIPN more frequently than normal/underweight patients (12% and 10%, respectively); both groups had similar discontinuation rates for BIPN (obese 13%, normal/underweight 8%).

Conclusion

Obese patients were found to be at higher risk for the development of BIPN compared to non-obese patients. Future studies should answer the question if lifestyle modifications including exercise and weight management during B treatment may influence the incidence of BIPN.