Bortezomib, Doxorubicin and Dexamethasone (PAD) Combination Therapy for Chinese Relapsed or Refractory Multiple Myeloma.

To investigate the efficacy and safety of PAD (bortezomib, doxorubicin and dexamethasone) combination therapy for Chinese relapsed or refractory multiple myeloma (MM).

31 patients with relapsed or refractory MM received two to eight 21-days cycles of PAD: comprising an intravenous bolus of bortezomib 1.3 mg/m² (P₁,N=13) or 1.0 mg/m² (P₂,N=18) on days 1, 4, 8, and 11, doxorubicin 10mg per day on days 1 to 4, along with dexamethasone 40mg on days 1-4. Response to PAD was evaluated according to International Myeloma Working Group Criteria (IMWG 2006), toxicity was graded according to NCI CTCAE v3.0.

25 patients (80.6%) achieved at least a partial response (PR), including complete response (CR) in 9 patients (29%), very good partial response (VGPR) in 7 patients (22.6%), PR in 9 patients (29%) and stable disease (SD) in 4 patients(12.9%), progression of disease (PD) in 2 patients (6.5%); median time to progression was 9.2 months, the median courses to achieve at least PR was 1.6(1-3) cycles, all of 7 patients with extramedullary plasmacytoma achieved at least PR after the first cycle of PAD, extramedullary plasmacytoma disappeared with 1-2 cycles of PAD. The efficacy was independent of traditional prognostic factors such asβ2-MG, Albumin,LDH and Hemoglobin which have previously influenced response to traditional chemotherapy. 1.5 year OS (Overall survival)of CR+VGPR group and PR group were 87.5% vs 46.7% (P=0.09). ≥PR response rate (CR +VGPR +PR) of P₁AD and P₂AD were 84.6% VS 77.8% (P= 0.501), CR+VGPR rate of P₁AD and P₂AD were 53.8% vs 50.0% (P=0.561 ). 1 year PFS(Progession-free survival) of P₁AD and P₂AD were 61.2% vs 55.6%(P=0.638), there were not difference between P₁AD and P₂AD in response rate(P= 0.501) and 1 year OS (P=0.872). Adverse events included thrombocytopenia in 15 patients ( 48.4% ), leukopenia in 8 patients(25.8%), peripheral neuropathy in 6 patients (19.4% ), varicella herpes zoster in 7 patients (22.6%), fatigue in 11 patients (35.5%) and diarrhea in 5 patients (16.1%), Thrombocytopenia and peripheral neuropathy of P₁AD and P₂AD were 46.2% vs 11.1%( P=0.037)and 53.8% vs 11.1%(P= 0.014).Common adverse reactions could be controlled with routine supportive treatmemt, one patient (3.2% ) died from respiratory failure during his fifth P₁>AD.

PAD should be considered an appropriate treatment for Chinese relapsed or refractory MM, especially for MM with extramedullary plasmacytoma, its efficacy were independent of traditional prognosis factors, bortezomib dose reduction may reduce toxicities of PAD while retaining the efficacy.

No relevant conflicts of interest to declare.