Bortezomib Plus Dexamethasone in Relapsed/Refractory Multiple Myeloma. Evaluation of the Efficacy and Toxicity

BACKGROUND: Bortezomib is a reversible proteasome inhibitor with activity in multiple myeloma (MM). Durable responses have been reported when administered as monotherapy or in combination therapy for relapsed or refractory MM, without severe toxicity. The latest studies prove a 43% response rates in patients in monotherapy who had received 1–3 prior treatment schedules.

AIM: To evaluate the efficacy of bortezomib plus dexamethasone in patients with relapsed or refractory MM (primary end point). As secondary objective, we evaluated the toxicity profile, time to progression (TTP), time to alternative treatment (TTAT) and overall survival (OS).

PATIENTS AND METHODS: We evaluated 192 patients with relapsed or refractory MM from seven Andalusian hospitals since January 2004 until June 2008. Patients received 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 3-week, for up to 8 cycles. Our series median age was 61 years (range 36–84) and included 49% males. The median follow-up period was 14.1 months (0.8–42.2). The prognostic markers recorded at the time of diagnosis were: beta2-microglobuline >3,5 mg/l (53.6 %), albumine <3.5 g/dl (61.4%), mean of plasma cells in bone marrow (35.6 ± 2%) and ISS stages at diagnosis (stage I 31%, stage II 31%, stage III 38%). The incidence of plasmacytoma was 23.5%. The median number of therapies prior to Bortezomib-Dexamethasone was 1 (range 1–8) and 8.3% patients had previously undergone autotransplant. Response was evaluated according to the modified EBMT criteria after 4th and 8th courses. Adverse events were graded based on WHO toxicity scale.

RESULTS: 165 patients were analyzed after 4 cycles. Overall response (OR) considered as partial response (PR) or better, was achieved by 69.7%; complete response (CR) by 11.5%; near complete response (CnR) 8.5%; PR 49.7%; minimal response (MR) 3.6%; stable disease (SD) 8.5% and progression 7.9%. At the end of the 8th cycle we evaluated 120 patients and found the following responses: OR: 58.3%; CR 14.2%; CnR 18.3%; PR 25.8%; MR 2.5%; SD 5% and progression 6.7%. The OS was 66.1%. In patients who progressed, the median of TTP was 10 months (1–33) and the median of TTAT was 12 months (1–36). The toxicity profile (grade 3–4) was: thrombocytopenia 34%, anemia 10%, neutropenia 9%, gastrointestinal 21% and neuropathy 31%. Forty percent of patients required bortezomib dose reduction whereas dexamethasone was ajusted in 10.9% of patients, because of toxicity or intolerance.

CONCLUSION: Bortezomib is an effective agent with acceptable toxicity for the treatment of patients with relapsed/refractory MM. The response rates, overall survival and toxicity in our series are similar to data described in previous studies, although a longer follow up is needed in order to confirm these results.