Bortezomib Plus Dexamethasone as Second Line Therapy after Vincristine, Adriamycin and Dexamethasone in Multiple Myeloma

BACKGROUND: Bortezomib is an useful drug for the second line treatment of Multiple Myeloma (MM). This reversible proteasome inhibitor obtains durable responses in relapsed or refractory MM, given as monotherapy or in combination, with acceptable toxicity.

AIM: To analyse the overall response of bortezomib plus dexamethasone in patients with relapsed or refractory MM after treatment with vincristine, adriamycin and dexamethasone (VAD) regimens. The time to progression (TTP), time to alternative treatment (TTAT), overall survival (OS) and toxicity profile were also studied.

PATIENTS AND METHODS: We conducted a retrospective study of 58 patients with relapsed or refractory MM from seven Andalusian hospitals since March 2005 until June 2008. Patients received bortezomib and dexamethasone as second line therapy after a prior treatment with VAD regimens. The patients were treated with standard bortezomib dose (1.3 mg/m2 IV bolus on days 1, 4, 8 and 11) plus dexamethasone (40 mg/d PO the same days) every 21 days, for up to 8 cycles. The mean age of our series was 57 years (range 39–66) and included 53% males. The prognostic variables at the time of diagnosis were: beta2-microglobuline >3,5 mg/l (57 %), albumine <3,5 g/dl (41%), mean of plasma cells in bone marrow (37 ± 3,6%) and ISS stages at diagnosis (stage I 29%, stage II 28% and stage III 43%). The incidence of plasmacytoma was 22%. Response was evaluated according to the modified EBMT criteria after 4th and 8th courses. Adverse events were graded based on WHO toxicity scale.

RESULTS: Fifty-eight patients with refractory/relapsed MM after VAD were analysed with a median follow-up of 11.6 months (1.5–40.5). Forty-eight patients (83%) were evaluated after 4 cycles and the overall response (OR), considered as partial response (PR) or better, was 70.9%; complete response (CR) 18.8%; near complete response (CnR) 18.8%; PR 33.3%; minimal response (MR) 2.1%; stable disease (SD) 12.5% and progression 8.3%. Thirty-three patients (57%) received 8 cycles and the analysis showed the following responses: OR 63.7%, CR 9.1%, CnR 27.3%, PR 27.3%, SD 6.1% and progression 12.1%. In patients who progressed, the median of TTP was 9 months (4–20) and the median of TTAT was 9 months (5–22). Grade 3–4 anemia, neutropenia and gastrointestinal toxicity were not observed in our series. Thrombocytopenia and neuropathy (grade 3–4) appeared in 3% and 11% respectively. Thirty percent of patients required dose reduction of bortezomib whereas dexamethasone was ajusted in 11% of patients, because of toxicity or intolerance. The overall survival of the series was 76%.

CONCLUSION: The combination of bortezomib and dexamethasone is an effective alternative of second line treatment without severe toxicity in patients with refractory/relapsed Multiple Mieloma.