Addition of Bortezomib (Velcade^™) to High Dose Melphalan (Vel-Mel) as an Effective Conditioning Regimen with Autologous Stem Cell Support in Multiple Myeloma (MM).

Velcade has shown promising activity alone and, more recently, in combination with other anti-myeloma agents (dexamethasone, thalidomide, doxil, standard dose melphalan) for relapsed or refractory multiple myeloma. We have now explored the efficacy and safety of Velcade™ 1.0 or 1.3mg/m² administered on days -4 and -1 prior to Melphalan, which was given in two fractionated doses for a total of 100–250 mg/m² on days -4 and -1 or as single dosing on day -1 supported on day 0 by PBSC infusion. Follow-up is now 1–5 months; detailed follow-up data will be available at presentation. Of 37 patients currently evaluable for toxicity, 27 are also evaluable for response. Patient characteristics are outlined in Table 1, depicting a high risk population.

The treatment was administered in the out-patient setting in 37 patients, 27 of whom were entirely managed through ambulatory care. Hospital admission was required for pneumonia in 4, sepsis in 3, nausea and vomiting in 2 and ileus in 1 patient. In 37 evaluable patients, hematopoetic recovery depended upon the timing of PBSC collection (prior to the first, second or the Vel-Mel transplant). Neutrophil recovery to > 1,000/μL occurred at a median of 13 days and platelet recovery to 50,000/μl at a median of 17 days. Non-hematologic toxicities included ≥ grade III mucositis in 5, diarrhea in 11, febrile neutropenia in 5, pneumonia/sepsis in 14, and fatigue in 22 patients. No fatal complications were seen.

Of 27 evaluable patients, partial response (≥ 75% of serum M protein reduction, ≥ 75% of urinary M excretion) was obtained in 9 (39%) including 6 (26%) who showed a complete disappearance of serum M and urine M. Bone marrow follow-up examinations were available in 17 patients and revealed a median reduction in plasmacytosis of 75% including 2 patients achieving a normal bone marrow plasmocytosis

Our results are promising and demonstrate that Vel can be safely added to Mel at doses as high as 250 mg/m² in fractionated dosing with a high response rate also in high-risk, advanced disease. This approach will be formally evaluated in a randomized trial comparing tandem transplants with Mel 200 mg/m² alone versus added Vel 1.0 mg/m² on days 1 and 4 followed on each day by Mel 140 (total 280 mg/m²).