Once-Weekly 1.6 mg/m2 Bortezomib BCD Regimen in Elderly Patients with Newly Diagnosed Multiple Myeloma Who are Unfit for Standard Dose Chemotherapy

Abstract

Bortezomib has shown anti-myeloma effects in combination with alkylating agents, but clinical benefits can be limited by neurotoxicity. There is less information on the efficacy and tolerability of once-weekly 1.6 mg/m 2 bortezomib combined with cyclophosphamide and dexamethasone (BCD) regimen in elderly patients with newly diagnosed multiple myeloma who are unfit for standard dose chemotherapy. Here, we report our experience of weekly 1.6 mg/m 2 intravenous bortezomib in this group of patients. Between March 2010 and February 2015, we treated 34 newly diagnosed elderly patients with the combination of bortezomib 1.6 mg/m 2 intravenously on days 1 and 8; cyclophosphamide 200 mg/m 2 intravenously on days 1-4; dexamethasone 20 mg intravenously on days 1-4, and 8-11. Among the 34 patients, 14 (41 %) responded with complete response (CR), 6 (18 %) with very good partial response (VGPR) and 10 (29 %) with partial response (PR). The overall response rates were 88 %. After 2 cycles of treatments, the survival of patients who attained a response of VGPR or CR was significantly longer than those with PR or resistance to BCD, for both progression-free survival (PFS) (21.4 vs. 10.6 months, p = 0.002) and overall survival (OS) (23.0 vs. 16.8 months, p = 0.043). The 2-year PFS and OS were 26.5 and 64.7 % respectively in these elderly multiple myeloma patients in our study. Grade 1/2 neuropathy was observed in 20 % of the cycles while grade 3/4 neuropathy was not observed. No patients withdrew due to neuropathy or other side effects. Onceweekly bortezomib at 1.6 mg/m 2 BCD regimen is both effective and safe in elderly patients with newly diagnosed multiple myeloma who are unfit for standard dose chemotherapy.

Daratumumab, cyclophosphamide, bortezomib, and dexamethasone for transplant-ineligible myeloma: AMaRC 03-16

“…In the context of the VCD regimen, weekly delivery of bortezomib has been reported in transplant-eligible populations, 21 , 22 , 23 , 24 but there have only been a few small retrospective reports of a weekly VCD regimen for the initial treatment of older patients. 25 , 26 The schedule of VCD in our trial, using 4-weekly bortezomib doses in a 5-week cycle, proved highly tolerable despite the older and frail population. Approximately 80% of patients in the VCDD arm completed the planned 9 cycles of induction, with an all-grade peripheral neuropathy rate of 28% and no grade 3 or 4 events.…”

Once-weekly bortezomib had similar effectiveness and lower thrombocytopenia occurrence compared with twice-weekly bortezomib regimen in treating patients with newly diagnosed multiple myeloma in China

“…[33] Hence, the aim of alternative bortezomib regimens is to reduce adverse reactions while ensuring efficacy. [19,34] So far, the studies suggest that the efficacy of the bortezomib once weekly regimen is relatively good and with low toxicity in patients with MM, [22,25–27] but data are still lacking in various populations.…”

“…[7,8,21,22] Although the standard bortezomib regimen shows more significant effects than the traditional chemotherapy regimens, its adverse reactions including thrombocytopenia, leukopenia, severe peripheral neuropathy (PN), gastrointestinal reactions, herpes zoster, and various infections [23] often lead to the reduction of the dose and even to the termination of treatment, affecting the efficacy and prognosis. [24] Therefore, alternative less toxic regimens are being sought, such as changing from twice weekly to once weekly [22,25–27] or from the traditional intravenous administration to subcutaneous injection. [28,29] So far, the studies suggest that the efficacy of the bortezomib once weekly regimen was relatively good and with low toxicity.…”

Discriminating Depth of Response to Therapy in Multiple Myeloma Using Whole-body Diffusion-weighted MRI with Apparent Diffusion Coefficient

“…With the introduction of novel therapeutics including immunomodulatory agents (thalidomide, lenalidomide) and proteasome inhibitors (bortezomib), the prognosis of patients with MM has significantly improved. Recent studies have confirmed the significance of deep response particularly complete response (CR) or very good partial response (VGPR) to induction therapy for patients with newly diagnosed MM (4)(5)(6).…”