Pegylated Liposomal Doxorubicin (PLD), Vincristine and Reduced-Dose Dexamethasone (DVd) in the Treatment of Predominantly African American Population with Multiple Myeloma.

Biologic therapy is emerging as first line therapy for multiple myeloma. However, most patients will require multiple lines of treatments and chemotherapy remains a very good option. In the last few years, there has been an important recognition of potentially different responses to pharmaceuticals based on genetic predisposition, starting with the FDA advisory panel recommending approval of a heart failure drug for African Americans. Liposomal doxorubicin (DOXIL; PLD) is a microscopic pegylated phospholipid vesicle with a core containing conventional doxorubicin. The pegylated coat protects the liposomes from detection by mononuclear phagocytes, increasing blood circulation time (t1/2=55 hours). Due to its prolonged half life, PLD provides a similar effect to using continuous infusion doxorubicin, but administered over 1-hour, transforming the regimen into an outpatient treatment. PLD has also been shown to have a significantly better safety profile than conventional doxorubicin. We evaluated the efficacy and safety of DVd in a predominantly African American population. A phase II trial using DVd was started in October 2000(PLD 40 mg/m2, vincristine 2 mg IVP and dexamethasone 40 mg PO 1-4 d every 4-weeks). Thirty-four patients have received DVd (15 males/19 females: mean age 59 years [range 42–77]) (five patients were off-study but received DVd per protocol). The majority of patients are African American (70%), a patient population not commonly studied. Patients presented with relatively advanced disease (stage II–III). Baseline mean serum albumin level was 3.5 mg/dl (range 1.8 to 4.9), beta-2 microglobulin 4.09 (range 1.0–8.97). Seventeen patients had IgG Kappa, seven patients had IgG lambda, six patients had IgA and four patients had light chain disease. Twenty five patients completed six cycles of therapy, with two patients completing five cycles. Six patients underwent autologous bone marrow transplant following their response to DVd. Response was assessed on the basis of a reduction of the paraprotein in serum or urine that lasted for at least six weeks. A response was achieved in 27 patients of whom 15 had a CR or nCR. 2 patients had stable disease, and disease progressed in four patients based on Blade Response Assessment. One patient died before response could be assessed. Median follow up is 36 months (range 3 months to 5 years). Our median time to progression is approximately 1 year. Twenty four patients are still alive, one patient has been lost to follow up and nine deaths have occurred. Four early deaths were due to disease progression and sepsis. Three of the early deaths had amyloidosis. Two died after one year of therapy due to progressive refractory disease. One died after the second cycle because of sudden cardiac death with sepsis. No episodes of cardiac dysfunction were observed. For African Americans, who have a high incidence of hypertension, renal and cardiovascular disease, a cardiac safer liposomal doxorubicin may be the preferred form of anthracyline.