Frail elderly patients with relapsed-refractory multiple myeloma: efficacy and toxicity profile of the combination of bortezomib, high-dose dexamethasone, and low-dose oral cyclophosphamide

Weekly intravenous bortezomib is effective and well tolerated in relapsed/refractory myeloma

“…Two smaller studies of 16 and 18 patients each, respectively, again with biweekly bortezomib, reported ORR of 75% (20) and 83% (21). Notably, in the former study (20), 38% of patients had treatment discontinuation and 31% treatment delays for PN, whilst that latter study (21) reported 17% grade 4 PN and 17% dose reductions for grade 2/3 PN. The lower neurotoxicity in the MD Anderson study (19) may relate to the fact that many of their patients transferred to a weekly bortezomib regimen after three cycles.…”

“…A MD Anderson study reported an overall response rate (≥PR) of 73%, with a PN incidence of 55% (grades 1–2) in 44 patients treated with cyclophosphamide on days 1–4, together with biweekly bortezomib 1.3 mg/m 2 on days 1, 4, 8 and 11 and dexamethasone 20 mg on days 1–4, 8–11 and 17–21 of a 4‐week cycle . Two smaller studies of 16 and 18 patients each, respectively, again with biweekly bortezomib, reported ORR of 75% and 83% . Notably, in the former study , 38% of patients had treatment discontinuation and 31% treatment delays for PN, whilst that latter study reported 17% grade 4 PN and 17% dose reductions for grade 2/3 PN.…”

Successful Use of Cyclophosphamide as an Add-On Therapy for Multiple Myeloma Patients with Acquired Resistance to Bortezomib or Lenalidomide

“…The addition of CY to thalidomide (CTD (CY, thalidomide and dexamethasone)) [20, 21], lenalidomide (CRD (CY, lenalidomide and dexamethasone), REP (lenalidomide, CY and PSL)) [15, 16, 22], or bortezomib (CyBorD (CY, bortezomib and dexamethasone)) [17, 18, 23] has been shown to increase better response rates and possibly prolong survival of patients with newly diagnosed MM or RRMM. Thus, the addition of CY enhances the therapeutic effects of novel agents in myeloma patients.…”

“…A series of clinical trials in the UK in the 1980s demonstrated the equivalent efficiency of cyclophosphamide (CY) to melphalan and highlighted its favorable toxicity profile, with less profound myelosuppression and lack of stem cell toxicity, compared to melphalan [14]. In addition, CY has been studied in combination with lenalidomide or bortezomib for relapsed disease, with excellent efficacy and safety [15–18]. However, it remains uncertain whether add-on therapy with CY is effective for MM patients who progressed or relapsed during treatment with novel agents.…”

Bortezomib-Cyclophosphamide-Dexamethasone for Relapsing Multiple Myeloma

“…[10][11][12] In vitro studies have shown synergistic antimyeloma effects with the combination of bortezomib and an alkylating agent through multiple mechanisms. 13,14 Consequently, combinations of bortezomib, cyclophosphamide, and dexamethasone (BCD) are rational with the prospect of independent toxicity, [15][16][17][18] as are similar programs where melphalan had been substituted for cyclophosphamide. 19,20 Therefore, we assessed the value of a BCD combination in 44 patients with relapsing myeloma.…”