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

Recently there has been an important recognition of potentially different responses to pharmaceuticals based on genetic predisposition, with the first FDA advisory panel recommending approval of a heart failure drug for African Americans alone. 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 (t½ = 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 cardiac safety profile than conventional doxorubicin. A phase II trial using DVd was started in October 2000 and is still enrolling (PLD 40 mg/m², vincristine 2 mg IVP, and dexamethasone 40 mg PO 1–4 d every 4-weeks). Twenty-seven patients have been enrolled (11 males/16 females; mean age 56 years [range 41–75]). The majority of patients enrolled in this study are African American (74%), a patient population not commonly studied. Patients presented with relatively advanced disease (stages II – III). Baseline mean serum albumin level was 3.5 mg/dL (range 1.4 to 4.4), beta-2 microglobulin 3.38 (range 1.0 – 8.97), fourteen patients had IgG Kappa, three patients has IgG Lambda, six patients with IgA, and four patients with light chain disease. Eighteen patients completed six cycles of therapy, with two patients completing five cycles. Six patients underwent autologous bone marrow transplant following their response to DVd.

CR, and nCR was achieved in nine patients, partial responses were achieved in seven patients, minor response in two patients, and progressive disease in five patients, based on Blade Response Assessment. Median follow up is twenty-four months (range 3 months – 5 years). Overall medium time to progression is approximately 1 year. Twenty patients are still alive, one patient has been lost to follow up, and six deaths have occurred. Four early deaths were due to disease progression and sepsis. 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. Three of the early deaths had amyloidosis. No episodes of cardiac dysfunction were observed.

Conclusion: African Americans have a 3-fold higher risk of cardiac toxicity with conventional doxorubicin. The use of DVd in this predominantly African American patient population was cardiac safe and provided an easy administered outpatient option, with an overall response rate of ~66% in stage II–III patients.