Bortezomib (BZB)-associated adverse events (AE) in patients with multiple myeloma (MM).

Abstract

e18565 Background: In patients (pts) with MM, BZB therapy causes AE, some of which may be related to autonomic nervous system (ANS) dysfunction. Methods: We conducted a retrospective case control study of 5 pts, with pts serving as their own control. Each pt received 2 cycles of BZB-containing regimens (BZB with Dexamethasone and either Thalidomide or Lenalidomide). One of the two treatment courses used high-dose (HD) BZB (1.6 mg/m2, higher than the standard 1 to 1.3 mg/m2), while low-standard (LD) dose (0.7, 1.0 or 1.3 mg/m2) was applied during the other cycle. The medical records of these pts were reviewed, including for AE that are typically associated with ANS dysfunction like orthostatic hypotension, pyrexia (≥ 1020), severe diarrhea and severe constipation. Orthostatic hypotension was used as a measurable toxicity parameter with statistical comparison of its incidence (Pearson Chi Square test) between three groups: 1) pre-BZB therapy (control); 2) LD and 3) HD BZB cycles. Results: Cycles of LD BZB were well tolerated in all 5 patients in contrast to poor toleration in 4 of the 5 HD BZB cycles which required aggressive medical management for severe dizziness (1 pt) and hospitalization in 3 pts: 1) severe constipation and pyrexia(≥ 1020); 2) severe diarrhea, orthostatic hypotension and dizziness and 3) severe orthostatic hypotension. A specific etiology for these AE could not be identified despite a comprehensive work-up. The AE normalized by day 0 of the second cycle. Orthostatic hypotension was observed in 3 of 5 and 5 of 5 of LD and HD BZB cycles respectively versus 0 of 5 in the control group. A significant incidence of orthostatic hypotension was observed with HD BZB vs. control (α = 0.0079; α<0.05 is significant) and with both BZB groups combined vs. control (α= 0.0093). Conclusions: HD BZB therapy is associated with otherwise unexplained, but transient orthostatic hypotension, pyrexia, and severe diarrhea and constipation. These findings are classically observed in ANS disorders, suggesting that some of BZB-related AE may be caused by transient ANS dysfunction.