Bortezomib, doxorubicin and dexamethasone (PAD) front‐line treatment of multiple myeloma: updated results after long‐term follow‐up

Abstract

SummaryBortezomib, doxorubicin and dexamethasone (PAD) was evaluated as induction before stem cell transplantation in newly diagnosed multiple myeloma (MM) patients, using bortezomib 1AE3 mg/m 2 (PAD1, N = 21) or 1AE0 mg/m 2 (PAD2, N = 20). Complete/very good partial response rates with PAD1/PAD2 were 62%/42% postinduction and 81%/53% post-transplant. Progression-free survival (29 vs. 24 months), time to re-treatment (36 vs. 29 months) and overall survival (1 year: 100% vs. 95%; 2 years: 95% vs. 73%) were statistically similar but favoured PAD1 versus PAD2. Toxicity was lower in PAD2; bortezomib dose reduction may help manage toxicities while retaining efficacy. PAD is highly active as front-line induction in MM.

Management of Newly Diagnosed Symptomatic Multiple Myeloma: Updated Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) Consensus Guidelines 2013

“…73 The regimen was very well tolerated, with a low rate of neuropathy; similar results were seen in another trial using the same combination. 82 The combination of cyclophosphamide, bortezomib, and dex was associated with a high ORR and deep responses in 2 different studies. 74,75 Reeder et al 75 observed an ORR of 88%, with 61% VGPR and 39% CR or near-complete response (nCR), when administering this combination every 28 days, and no adverse impact on stem cell collection was noted.…”

Lenalidomide, bortezomib, pegylated liposomal doxorubicin, and dexamethasone in newly diagnosed multiple myeloma: a phase 1/2 Multiple Myeloma Research Consortium trial

“…4,6,7 Other 3-drug regimens producing high rates of CR and VGPR in patients with newly diagnosed MM include bortezomib, thalidomide, and dexamethasone (VTD) 5,8,9 ; cyclophosphamide, thalidomide, and dexamethasone (CTD) 10 ; bortezomib, cyclophosphamide, and dexamethasone (VCD) [11][12][13] ; and bortezomib, doxorubicin, and dexamethasone (PAD). 14 Furthermore, the 4-drug regimen of bortezomib, dexamethasone, cyclophosphamide, and lenalidomide (VDCR) has recently been shown to be highly active and generally well tolerated in patients with newly diagnosed MM, although some additional toxicity was noted. 15,16 We hypothesized that combining the 4 active drugs from the RVD and VDD regimens into one regimen, specifically RVDD (lenalidomide, bortezomib, PLD, and dexamethasone) might further increase CR/nCR and VGPR rates and thus potentially improve outcome.…”

Multiple myeloma and persistence of drug resistance in the age of novel drugs (Review)

“…Other novel agents like thalidomide derivatives (lenalidomide) and proteasome inhibitor (bortezomib) combination chemotherapy increases the overall response rate to 90% or above (109)(110)(111)(112).…”