A recent study in the Journal of Clinical Oncology reports that the combination therapy of Velcade (bortezomib), thalidomide (Thalomid), and dexamethasone (Decadron), commonly referred to as VTD, was successful at improving response and eliminating residual cancer cells in multiple myeloma patients after autologous stem cell transplantation (ASCT).

In ASCT, the patients’ own stem cells that were collected before high-dose chemotherapy are transplanted back into the patients. Most myeloma patients retain a small number of cancerous cells in their blood and bone marrow after ASCT. These cells are a major cause of relapse. At the same time, they are difficult to detect by most techniques because of their small number. They can, however, be detected by a sensitive biological technique known as polymerase chain reaction (PCR).

The study authors hypothesized that new agents such thalidomide, Revlimid (lenalidomide) and Velcade, may be effective in further reducing the number of tumor cells surviving in the marrow after ASCT to levels only observed with allogeneic stem cell transplantations. In allogeneic stem cell transplantations, patients receive bone marrow from a donor.

To verify their hypothesis, the researchers recruited 39 newly diagnosed multiple myeloma patients under the age of 70 who had reached at least a very good partial response after ASCT. None of the patients had been previously exposed to thalidomide or Velcade.

For treatment, patients received four cycles of Velcade (1.6 mg/m² intravenously on days 1, 8, 15, and 22 followed by a 13 day rest period), thalidomide (50 mg per day orally with 50 mg weekly increments up to 200 mg per day until treatment completion), and dexamethasone (20 mg per day orally on days 1 to 4, 8 to 11, and 15 to 18, followed by a 17-day rest period).  All patients received at least one cycle of VTD. Thirty one patients (80 percent) completed all four cycles.

The researchers found that 49 percent of patients achieved a complete response after VTD therapy, compared to 15 percent of patients after ASCT.

Eighteen percent of patients achieved molecular remission, detected by PCR; this indicated that there was no evidence of myeloma cells in the blood or bone marrow after VTD therapy. All of these patients had received the full four cycles of treatment, and after 42 months, none had relapsed. Those patients in the study who did not complete the full course of treatment did not achieve molecular remission.

Twenty-one patients (54 percent) experienced severe side effects including infections, fatigue, low platelet count, and nerve damage to the limbs which lead the researchers to reduce the dose for both Velcade and thalidomide.

The researchers concluded that VDT therapy was effective in improving response and further reducing tumor cells in myeloma patients after ASCT.  They suggested that therapies after ASCT could be further improved by including Revlimid, as it may increase effectiveness and decrease side effects.

For more information, see the study in the Journal of Clinical Oncology (abstract).