Once Weekly Bortezomib Plus Dexamethasone in Newly Diagnosed Multiple Myeloma: A Preliminary Study in Chinese Patients

Bortezomib has become a cornerstone in the management of multiple myeloma (MM) and the currently accepted practice is a twice weekly administration at 1.3mg/m². Recently, several studies have demonstrated a successful treatment with the modified Bortezomib schedule in refractory or elderly newly diagnosed MM. These previous studies suggest that, given at weekly intervals, Bortezomib remains equally efficacious and may even improve tolerability. We here present our institution's experience where we retrospectively compare the efficacy and toxicity parameters between once weekly (1.6mg/m²) and twice weekly (1.3mg/m²) schedule of Bortezomib plus Dexamethasone in newly diagnosed, untreated MM patients.

The once weekly schedule consisted of 5-week cycle of which Bortezomib plus Dexamethsone was administered during the first 4 weeks as follows: Bortezomib 1.6mg/m² intravenously on days 1, 8, 15, 22 and Dexamethsone 20mg intravenously on days 1–2, 8–9, 15–16 and 22–23 followed by a 12-day rest period. The twice weekly schedule consisted of 3-week cycle as follows: Bortezomib 1.3mg/m² intravenously on days 1, 4, 8, 11 and Dexamethsone 20mg intravenously on days 1–2, 4–5, 8–9 and 11–12 followed by a 9-day rest period. We retrospectively collected data from Jan 2009 to Dec 2010 of 37 patients with newly diagnosed MM who were either treated with once weekly schedule (n =13) or twice weekly schedule (n = 24). Allocation of patients to their respective treatment group was not randomized but rather on the basis of their means, after they were made fully aware that the once weekly schedule was still under evaluation.

The median age was similar between two schedules (53 years vs. 54.5 years, P=0.674). Both treatment groups received a median number of two cycles of chemotherapy. The median follow-up was also similar, being 12 months (range, 4–19) in the once weekly treatment group and 10.5 months (range, 2–19)in the twice weekly treatment group. In the standard twice weekly schedule, the overall response rate of 74.9% including 2(8.3%) CR, 8(33.3%) VGPR and 8(33.3%) PR, while 2(8.3%) patients had stable disease (SD) and 3(12.5%) had progressive disease (PD). Among the patients in the weekly schedule, 10 of 13 patients (77.0%) achieved at least PR with 30.8% at least VGPR. In addition, SD was observed in 1 patient (7.7%) and PD in another 1 patient (7.7%). The responses to treatment were not found to be statistically significant different in our study when comparing the once weekly schedule to the twice weekly schedule. The median time to the best response was 2 cycles (range,2–4) in the once weekly schedule as compared with 2.5 cycles (range,2–4) in the twice weekly schedule (P=0.564). The median survival was not reached in either schedule since the follow-up was not long enough. The median progression free survival (PFS) and duration of response (DOR) of the weekly schedule did not differ significantly from that of the twice weekly schedule (8 months vs. 10 months, P=0.545 and 6 months vs. 7 months, P=0.467; respectively). After a median follow-up of 12 months (range, 2–19), 2 patients (15.4%) in the weekly schedule and 4 patients (16.6%) in the twice weekly schedule had died (P=0.723) thus mortality in the two groups did not differ significantly. Over grade 3 of gastrointestinal symptoms were similar in the once weekly (16%) and twice weekly (20.5%) schedules. Peripheral sensory neuropathy was reported more frequently in the twice weekly schedule, including grade 1 in 4 patients (17%), grade 2 in 4 patients (17%), grade 3 in 3 patients (12.5%), and grade 4 in 1 patient (4%). While grade 1 neuropathy in 2 patients (15%), grade 2 in 1 patient (8%), grade 3 in 1 patient (8%) were reported in the weekly schedule and all had resolved within two months. All grade 3 and 4 hematologic toxic effects were more frequent in the twice- weekly schedule than in the weekly schedule (75% vs. 54%), as was over grade 2 of herpes zoster (16.5% vs. 8%). Incidence of over grade 2 rash remained low and was similar in the two schedules (both 8%). However the difference between the two schedules was not statistical significantly.

Our study provides additional evidence that the once weekly Bortezomib (1.6mg/m²) plus Dexamethasone schedule is active and well tolerated in the treatment of patients with newly-diagnosed multiple myeloma, with the similar efficacy and lesser toxicity compared with the twice weekly schedule.

No relevant conflicts of interest to declare.