DVd Regimen Reduces Events Requiring Hospitalization in Multiple Myeloma

July 1, 2002

CLEVELAND-Hospitalizations due to adverse events were less likely to occur among newly diagnosed multiple myeloma patients who received DVd (pegylated liposomal doxorubicin [Doxil]/vincristine/dexamethasone (than those who received VAd (vincristine/doxorubicin [Adriamycin]/reduced-dose dexamethasone). Early results from a randomized phase III trial were reported by Mohamad A. Hussein, MD, of the Cleveland Clinic. The data are very preliminary, as safety data could be collected on only 94 of 135 patients who are enrolled at 22 sites in the study (ASCO abstract 1107).

CLEVELAND—Hospitalizations due to adverse events were less likely to occur among newly diagnosed multiple myeloma patients who received DVd (pegylated liposomal doxorubicin [Doxil]/vincristine/dexamethasone (than those who received VAd (vincristine/doxorubicin [Adriamycin]/reduced-dose dexamethasone). Early results from a randomized phase III trial were reported by Mohamad A. Hussein, MD, of the Cleveland Clinic. The data are very preliminary, as safety data could be collected on only 94 of 135 patients who are enrolled at 22 sites in the study (ASCO abstract 1107).

Hospitalizations relating to adverse events occurred in 17 of 50 DVd patients and 16 of 44 VAd patients. Adverse events related to the regimen caused more extended hospitalizations in the VAd patients: 7 compared to 3 in the DVd arm of the study. Only 3% of DVd treatment cycles were associated with unscheduled hospital admissions compared to 42% of VAd cycles.

Dr. Hussein said efficacy results are not available because outcomes had been blinded in the phase III trial, which is still recruiting patients. He reported that a phase II pilot trial showed DVd to produce an overall response rate of 88% in newly diagnosed multiple myeloma patients. The median time to failure was 23.1 months, and 1-year and 2-year progression-free survival rates were 42% and 23%, respectively.

Patients on the DVd regimen receive 40 mg/m² of pegylated liposomal doxorubicin and 1.4 mg/m² (to a maximum of 2.0 mg) of vincristine intravenously on day 1 and 40 mg of dexamethasone by mouth on days 1 to 4. Patients on the VAd regimen receive 0.4 mg/day of vincristine and 9 mg/m²/day of conventional doxorubicin by continuous infusion plus 40 mg of dexamethasone by mouth for 4 days.

Both regimens are delivered in cycles repeated every 4 weeks until the patient has disease progression, toxicity becomes unacceptable, or a plateau phase is reached. Dr. Hussein said toxicity has not been a problem in the DVd regimen, which appears to be well tolerated. Ten DVd patients (20%) were reported to have gone on to transplantation after responding to therapy compared to four VAd patients (9%).

Dr. Hussein said the investigators believe myeloma is a perfect target for pegylated liposomal doxorubicin because the pegylated liposomal formulation of doxorubicin has high vascular activity and can attack the disease in the bone marrow where it grows. Another advantage is that pegylated liposomal doxorubicin can be delivered intravenously on an outpatient basis.

"Myeloma cells are slow to grow, and you want to expose them for a longer time to the drug," Dr. Hussein told ONI. "VAd is usually delivered by continuous infusion for 4 days, but with the Doxil you can have active drug for 90 days."

One surprise in the data so far is that 6% of the DVd patients but none of the VAd patients have had grade 3/4 nausea. "We are going back to see whether antiemetics were given in the hospital," Dr. Hussein said. Because patients receiving VAD spend 4 to 5 days in the hospital, they are observed and if not feeling well may be prescribed an antiemetic. DVd is administered on an outpatient basis.