Comparison of efficacy from two different dosing regimens of bortezomib: an exposure–response analysis. (18th February 2020)

• Record Type: Journal Article
• Authors: Parasrampuria, Dolly A.; He, Jianming; Zhang, Liping; Muresan, Bogdan; Hu, Peter; Nemat, Sepideh; Hashim, Mahmoud; Lam, Annette; Appiani, Carlos; Cavo, Michele; Dimopoulos, Meletios A.; San‐Miguel, Jesus; Mateos, Maria‐Victoria
• Is Part Of: British journal of haematology. Volume 189:Number 5(2020)
• Page Start: 860
• Page End: 868
• Publication Date: 2020-02-18
• Subjects: bortezomib -- exposure–response -- VISTA -- ALCYONE -- multiple myeloma; Hematology -- Periodicals; Blood -- Diseases -- Periodicals; 616.15
• DOI: 10.1111/bjh.16446
• Languages: English
• ISSNs: 0007-1048

Abstract

Summary: Bortezomib is a first‐in‐class proteasome inhibitor, approved for the treatment of multiple myeloma. The originally approved dosing schedule of bortezomib results in significant toxicities that require dose interruptions and discontinuations. Consequentially, less frequent dosing has been explored to optimise bortezomib's benefit–risk profile. Here, we performed exposure–response analysis to compare the efficacy of the original bortezomib dosing regimen with less frequent dosing of bortezomib over nine 6‐week treatment cycles using data from the VISTA clinical trial and the control arm of the ALCYONE clinical trial. The relationship between cumulative bortezomib dose and clinical response was evaluated with a univariate logit model. The median cumulative bortezomib dose was higher in ALCYONE versus VISTA (42·2 vs. 38·5 mg/m 2 ) and ALCYONE patients stayed on treatment longer (mean: 7·2 vs. 5·8 cycles). For all endpoints and regimens, probability of clinical response correlated with cumulative bortezomib dose. Similar to results observed for VISTA, overall survival was longer in ALCYONE patients with ≥ 39·0 versus < 39·0 mg/m 2 cumulative dose (hazard ratio, 0·119; P < 0·0001). Less frequent bortezomib dosing results in comparable efficacy, and a higher cumulative dose than the originally approved bortezomib dosing schedule, which may be in part be due to reduced toxicity and fewer dose reductions/interruptions.