Background. Bortezomib, Melphalan and Steroids are among the most effective drugs for treatment of myeloma, and their combination has already been tested in elderly myeloma patients. However, in order the take full advantage of the synergy among these drugs, we designed a protocol for previously treated multiple myeloma patients consisting of six monthly courses of concurrent intravenous administration of the three drugs.

Methods Bortezomib was given at dosage of 1.3 mg/m2, Melphalan 5 mg/m2 and Dexamethasone 40 mg i.v. on days 1, 4, 8, 11 plus dexamethasone 40 mg per os on days 2, 5, 9, 12 (VMD). In total, 21 previously treated patients have been enrolled in this study, 9 males and 12 females. Median age was 64.5 (range 53–82). All patients had been already treated with a median of 2 previous lines of treatment (range 1–6), including HDT with ASCT in 7 patients and Bortezomib, alone or in combination, in 5 patients. Fourteen patients were resistant to previous therapies and 7 were relapsed. All patients were ineligible for transplant procedures.

Results After a median follow up of 9 months (range 3–14), 12/21 (57%) patients were considered responders: according to International Myeloma Working Group Criteria. 4 patients achieved a complete remission (M-protein not detectable at IFE), 4 patients a very good partial remission, 4 patients a partial remission, 7 achieved a stable disease, 2 were not evaluable. The most common grade 3/4 adverse events included hematological toxicity: thrombocytopenia (30%), anemia (8%), leucopenia (7%), neutropenia (3%) peripheral neuropathy (14%), diarrhea (14%) and infection (5%). So far, 4 patients have stopped treatment for toxicity after 1, 3, 3, 4 courses. PFS at 10 months was 67% and survival at 12 months 94%. Since VMD is an effective treatment but limited by haematological toxicity, we have modified the schedule of the combination using concurrent intravenous administration of bortezomib, melphalan and dexamethasone on days 1, 8, 15, 22 and restarting at day 35. So far, 9 patients with a median age of 69 ys (range 48–79), (5 patients in 2nd line and 4 in 3th line of treatment) were enrolled, and after a median of follow up of 4 months (range 2–5), 8 patients are evaluable. After a median number of two cycles, 6/9 (67%) patients were considered responders: 3 patients achieved CR, 1 patients VGPR, 2 patients PR, 1 was in stable disease and 1 in PD (died after 2 courses). With the new schedule we have obtained a significant reduction of grade 4 haematological toxicity (0% vs 18%, p<0.04, Chi square test) and a better patients’ compliance.

Conclusions The intravenous concurrent administration of Bortezomib, Melphalan, and Dexamethasone is an highly effective regimen even for heavily pretreated myeloma patients. The weekly administration schedule seems to reduce the hematological toxicity while maintaining the efficacy of the combination.

Author notes

Disclosure: No relevant conflicts of interest to declare.