Bortezomib effective as induction for stem-cell transplant in multiple myeloma

NEW YORK (Reuters Health) - When patients with untreated multiple myeloma undergo stem cell transplantation, adding bortezomib (Velcade) to the induction protocol achieves a high complete response rate, a prolonged response and good efficacy, Italian researchers have found.

In an online paper in the Journal of Clinical Oncology, the researchers report on a phase II, open-label trial in which the proteasome inhibitor bortezomib was used along with doxorubicin and dexamethasone as induction therapy. Patients then underwent stem cell mobilization using cyclophosphamide and granulocyte colony-stimulating factor, followed by two courses of melphalan and autologous stem cell transplantation, and finally, consolidation and maintenance therapy using lenalidomide.

This sequential therapy, the researchers write, "is an attractive regimen to maximize the efficacy of autologous stem cell transplantation and may represent a new treatment paradigm."

Dr. Francesca Gay of the Azienda Ospedaliero-Universitario San Giovanni Battista in Turin, who is the second author on the paper, told Reuters Health by e-mail that this study was the first to follow a sequential approach using bortezomib for induction and lenalidomide for consolidation/maintenance in patients with newly diagnosed multiple myeloma.

She cautioned, however, that "these promising results" need to be confirmed in randomized trials.

Dr. Gay and her colleagues enrolled 102 patients with treatment-naïve multiple myeloma and a median age of 67. For induction, along with dexamethasone and pegylated liposomal doxorubicin, patients received bortezomib 1.3 mg/m2 given on days 1, 4, 8 and 11 of a 21-day cycle, for 4 cycles. Patients who did not have progressive disease 2 to 4 months after two cycles of melphalan and stem cells received 16 weeks of consolidation therapy with lenalidomide plus prednisone, followed by maintenance with lenalidomide alone.

Eighty-three patients received both cycles of melphalan plus the autologous stem cells, and 80 entered consolidation.

Responses were rapid, the authors said, with a least a partial response in 69% of per-protocol patients after the first 21-day induction cycle, and a very good partial or complete response in 58% by the end of induction.

The percentage of patients with at least a very good partial or a complete response grew to 82% following melphalan/stem cell therapy and to 86% after consolidation therapy, with a complete response in 66%.

After a median follow-up of 21 months, the 2-year progression-free survival rate was 69% and 2-year overall survival was 86%.

Seven deaths resulted from treatment-related adverse events. The most common serious adverse events were thrombocytopenia, neutropenia, peripheral neuropathy, and pneumonia.

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