Complete Remission Achievement during Long-Term Maintenance with Bortezomib Based Therapy in Multiple Myeloma: A Case Report.

The treatment of multiple myeloma (MM), a B-cell neoplasm characterized by a clonal expansion of plasma cell in the bone marrow, remains unsuccessful in a significant proportion of patients. The majority of MM patients fail to achieve a complete response (CR) with standard therapy. Bortezomib is a new drug that has been shown to induce a complete response (CR) in 10% of pre-treated patients and continues to show benefit in relapsing/refractory myeloma treatment. We report a case of 72 year-old women with IgAl and IgGK MM who resulted refractory to two different line therapies. Patient was diagnosed with MM in March 2005 following the admission to our clinic for bone pain and weight loss. Laboratory blood tests were: total protein 9,4 gr/dl; IgAl and IgGK monoclonal spike (IgG: 917; IgA: 2990, IgM<17, Ks: 253, ls: 997 gr/dl); Beta2 microglobulin 2,7 mg/L; Ca 9,7 mg/dl. Mild pancytopenia was found. No renal failure and significant proteinuria were observed, Bence Jones were negative. Bone scans revealed diffuse lytic lesions to spine with a vertebral fracture (D12). Bone marrow biopsy showed 60% of plasma cells, with atypical characteristics. Initial treatment consisted of melphalan, prednisone and pamidronate that were given for a total of four cycles. Patient achieved a stable disease according to International Myeloma Working Group criteria. Then the patient underwent idarubicine based regimen without any response indicating refractory MM. In November 2005, a 3-week cycle schema with Bortezomib (1,3 mg/m² i.v. on day 1,8,11), Melphalan (10 mg PO on day 1,3,5) and Dexamethasone (4 mg i.v. on day 1,8,11,15) was started. The patient achieved a partial response (PR) after 8 cycles of this combination therapy .No therapy related Grade 3–4 neuropathy and trombocytopenia were observed. The patient experienced a mild HZV reinfection. In June 2006, a maintenance regimen with Bortezomib (1,3 mg/m2 i.v. on day 1,8) Melphalan (6 mg PO on day 4,11) and Dexamethasone (4 mg i.v. on day 1,8,15) was initiated considering the positive response and the absence of toxicity from the primary previous therapy. Each cycle was repeated every three weeks for a total of 16 courses, until June 2007. Efficacy assessment (including bone marrow biopsy) was performed every three months and showed a sustained decrease in plasma cell infiltration and a persistent reduction of M serum protein.Very Good PR and CR were achieved after 10 and 16 maintenance courses, respectively. This case demonstrates that a Bortezomib-based regimen is effective and feasible in refractory MM and, interestingly, supports the hypothesis that a long-term maintenance therapy may improve the quality of response. This treatment approach should be evaluated in a larger patient cohort and in prospective randomised trials.