Intermediate Dose Melphalan, Bortezomib, Thalidomide, Dexametasone (MVTD) Conditioning Therapy and ASCT in Relapsed Multiple Myeloma Patients: A Single Center Experience.

Background: Autologous Transplantation with intermediate or high doses of Melphalan is the most effective therapy in patients with Multiple Myeloma being < 65 years old, although this procedure is limited by an high percentage of relapses. Recent advances knowledge of the molecular mechanisms, allowed the development of novel targeted therapies. Several studies have shown that the synergic effect of Bortezomib and Talidomidomide, in association with conventional chemotherapies, induces a more pronounced reduction of tumour mass, an enhancement of global responses and an improvement of Progression Free Survival (PFS).

Aims: The present study is aimed at the evaluation of effectiveness and toxicity of MVTD conditioning therapy with stem cell support in Multiple Myeloma relapsed patients.

Patients and Methods: From January 2005 to August 2007, 15 patients (7 males and 8 females: median age 62 yrs (46–70)) have been subjected to Autologous Transplantation therapy with MVTD conditioning therapy (Melphalan 100 mg/sqm days - 6 and - 3, Bortezomib 1.3 mg/sqm days - 6 and - 3, Talidomide 200 mg from day - 6 to day - 2, Desametazone from day - 6 to day - 3, CSP infusion at day 0). All patients were in CS III A; median performed therapies 3 (1–5); all had received previously a therapy with Talidomide, two Talidomide + Velcade, one PEG-IFN.

Results: 100% of patients obtained a response: 4 patients (26.7%) obtained CR, 5 (33.3%) a nCR, 4 (26.7%) a VGPR and 2 (13.3%) a PR. One patient in CR was subjected to 2 therapeutic lines and 3 patients in CR were subjected to more than 1 therapeutic lines, 5 in nCR from 2 to 4, 4 in VGPR from 2 to 4 and 2 in PR more than 2. At the moment, with a median of 7.5 months (1–21), 11 (73%) are alive, 8 (53%) still keep the obtained response, 3 (20%) after progression are in rescue therapy, 4 patients (27%) died because of progression. PFS median since MVTD beginning is of 6 months (1–24). None of the patients have developed a significant neurotoxicity. All patients have developed grade 4 thrombocytopenia and neutropoenia, with a median of 3 days (1–10) and 6 days (4–12), respectively. 54% of patients had neutropoenia with fever with a median of 2 days (0–8). The median units of platelets and red cells infused was 3 (2–11) and 2 (0–11), respectively.

Conclusions: In our experience, Autologous Transplantation therapy with MVTD conditioning, appeared to be effective in relapsed patients with Multiple Myeloma. Although in a small series of patients the response obtained was independent from the number and type of previous therapies, from the clinical state, and β2 microglobulin. No significant neurotoxicity has been observed, whether the haematological toxicity was overlapping to that due to conventional Autologous Transplant. Further studies, in larger series of non pluritreated patients are required.