Feasibility of cryocompression for bortezomib-induced peripheral neuropathy (BIPN) among patients with multiple myeloma (MM).
Authors: Statler Tiffany M. , Hsu Fang-Chi , Lambird Jonathan , Hurd David Duane , Cartwright Michael Stephen , Gandhi Mehta Rachana , Crisp James , Strowd Roy E. 
Published: June 2023

e24147

Background: BIPN is a dose-limiting side effect of bortezomib therapy occurring in over three-quarters of bortezomib-treated patients and results in increased morbidity secondary to decreased quality of life and increased mortality due to treatment discontinuation or dose-reduction. Cryocompression therapy acts at the level of the nerve and does not limit bortezomib anti-tumor activity, making it ideal for clinical testing in patients with BIPN. This study evaluated the feasibility of cryocompression therapy in MM patients with BIPN. Methods: MM patients with Common Terminology Criteria for Adverse Event (CTCAE) Grade 1-3 BIPN who previously received a bortezomib-containing regimen (Arm 1) or were currently receiving a bortezomib-containing regimen (Arm 2) were enrolled at a Comprehensive Cancer Center outpatient clinic. Patients were instructed to complete daily home cryocompression treatments on non-dominant hand and foot for 30 continuous minutes for 8-weeks. Primary outcome was compliance measured by device-recorded data and defined as completion of at least 25 of 30 minutes, 60% of prescribed treatment days. Change in patient reported symptoms was assessed by the European Organization for Research and Treatment of Cancer (EORTC) QLQ-CIPN20 questionnaire. Proportion of compliant patients was calculated. Spearman’s rank correlation coefficients were used to evaluate the association between treatment compliance and QLQ-CIPN20 scores. Here we report on Arm 1. Results: 12 patients (median age 63.9+11.8 years, 41.7% female, 66.7% white, 25.0% black) participated in Arm 1. 75% of patients were compliant. The mean proportion of treatment-compliant days was 65.8% (95% CI 46.5% – 85.0%). Patient-reported BIPN symptoms improved with QLQ-CIPN20 total and sensory sub scores of 39.2+9.2 and 22.5+4.7 at baseline, 33.7+6.2 and 19+3.5 at week 4, and 34.1+7.8 and 19.9+5.5 at week 8. This accounted for a statistically significant decline in total QLQ-CIPN20 score at week 4 (-5.9+9.1, p = 0.035), week 8 (-4.6+5.0, p = 0.020), and sensory sub score at week 4 (-3.5+3.4, p = 0.008) and week 8 (-2.6+3.5, p = 0.050). There was no correlation between compliance and change in total QLQ-CIPN20 score (r = -0.31, p = 0.380) or sensory sub score (r = -.054, p = 0.109) in the per protocol analysis (N = 10). Using a last-time-point available analysis, no correlation was observed for total QLQ-CIPN20 score (r = -0.44, p = 0.149) but a moderate-to-strong inverse correlation was observed between amount of cryocompression use and change in QLQ-CIPN20 sensory sub score (r = -0.62, p = 0.031). Conclusions: Cryocompression therapy is feasible in MM patients with BIPN who previously received a bortezomib-containing regimen. The observed biologic gradient with greater improvement in patient-reported sensory neuropathy with longer duration of cryocompression treatment supports the rationale and further study. Clinical trial information: NCT03870451 .