The results of a recent Japanese study suggest that a vincristine-doxorubicin-dexamethasone regimen without intermittent high-dose dexamethasone reduces the risk of bacterial infection in multiple myeloma patients without affecting the treatment’s efficacy. 

Based on these findings, the study authors recommended avoiding the administration of intermittent high-dose dexamethasone with the vincristine-doxorubicin-dexamethasone regimen in myeloma patients at high risk for infection. 

The combination treatment of vincristine (Oncovin), doxorubicin (Adriamycin), and dexamethasone (Decadron) plus high-dose pulses of dexamethasone (referred to as VAD-HD) was first approved as a treatment for advanced multiple myeloma.

It is currently also used in newly diagnosed multiple myeloma patients and can result in a high response rate of up to 80 percent in this patient population.  Additionally, VAD-HD has few effects on blood stem cells and is therefore often used as treatment for patients who plan to undergo stem cell transplantation.

Despite its efficacy, the VAD-HD regimen is associated with an increased risk of bacterial infections in multiple myeloma patients.  High doses of glucocorticoids, such as the dexamethasone included in VAD-HD, can suppress the immune system, making it more difficult for patients to fight off infections. 

In their retrospective analysis, the Japanese researchers sought to determine whether the omission of high-dose dexamethasone pulses from the VAD regimen could lower the rates of infection among multiple myeloma patients.

They analyzed data of 77 multiple myeloma patients who had been treated with either VAD or VAD-HD at their institution between July 1999 and October 2009. Of the 77 patients, 37 had received VAD alone, and 40 had received VAD-HD. 

Patients who were treated with VAD alone received 2-4 cycles of the drugs on days 1-4 of a 21-day cycle.  The VAD dosing schedule was identical for patients in the VAD-HD treatment group, with the addition of intravenous dexamethasone on days 9-12 and 17-20 of each 28-day cycle. 

The researchers found that there were no statistically significant differences in the overall response rates between the two treatment groups. Of the patients who received VAD without HD, 62.9 percent responded compared to 50 percent of patients who received VAD-HD. 

The researchers did find, however, that the VAD-HD treatment was associated with a higher risk of bacterial infection than the VAD treatment. They documented 26 bacterial infections in the patient group treated with VAD-HD, compared to 13 in the patient group treated with VAD.

Patients with more advanced stages of multiple myeloma were also at a higher risk of bacterial infection. The researchers documented 28 bacterial infections in patients with advanced stages of myeloma, compared to 11 in patients with early-stage disease.

The most commonly observed bacterial infections included pneumonia, urinary tract infections, and staphylococcus infections. 

For more information, please see the full study in the International Journal of Hematology (abstract).