For patients with newly diagnosed multiple myeloma who are transplant ineligible, bortezomib may be just as effective when given by way of a less frequent dosing regimen, according to an exposure-response analysis that compared data from the randomized phase 3 ALCYONE with VISTA trials. The analysis findings were recently reported in the British Journal of Haematology.
The standard dosing for bortezomib was approved on the basis of data from the VISTA trial (ClinicalTrials.gov Identifier: NCT00111319), and the data used in this analysis were from the patients enrolled in the treatment arm consisting of a regimen of bortezomib-melphalan-prednisone (VMP) over 9 treatment cycles, each lasting 6 weeks. Patients received bortezomib 1.3 mg/m2 intravenously twice per week for 4 cycles followed by once per week for 5 cycles.
The ALCYONE trial (ClinicalTrials.gov Identifier: NCT02195479) was conducted after the VISTA trial, and data used in this analysis were from patients enrolled in the control arm. These patients received a modified schedule of VMP over 9 treatment cycles, each lasting 6 weeks. Bortezomib was given less frequently and using a different route of administration than on the VISTA trial: 1.3 mg/m2 subcutaneously twice per week for 1 cycle followed by once per week for 8 cycles.
The analysis revealed a higher median cumulative dose of bortezomib among patients from the ALCYONE trial compared with the VISTA trial (42.2 mg/m2 vs 38.5 mg/m2). A cumulative dose of bortezomib of 39.0 mg/m2 or higher was shown to have lower likelihood of death or disease progression compared with a cumulative dose below 39.0 mg/m2 in both the VISTA (hazard ratio [HR], 0.434; 95% CI, 0.299-0.629; P <.0001) and ALCYCONE trials (HR, 0.280; 95% CI, 0.200-0.392; P <.0001).
Trials included several endpoints that assessed clinical response — namely, overall response rate, complete response rate, progression-free survival, and overall survival — and for both regimens, the probability of a clinical response was associated with a higher cumulative dose of bortezomib.
Patients from the ALCYONE trial received, on average, more treatment cycles (7.2 vs 5.8 cycles) and fewer patients from the ALCYONE trial stopped treatment early as a result treatment-emergent adverse events compared with patients from the VISTA trial (9% vs 15%, respectively).
“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,” the study authors wrote.
Disclosure: Some of the authors are employed by Janssen, and others disclosed financial relationships with pharmaceutical and medical device companies. For a full list of disclosures, please refer to the original study.
Parasrampuria DA, He J, Zhang L, et al. Comparison of efficacy from two different dosing regimens of bortezomib: an exposure-response analysis [published online February 18, 2020. Br J Haematol. doi: 10.1111/bjh.16446