Bortezomib in Combination with Pegylated Liposomal Doxorubicin and Thalidomide (VDT) for the Treatment of Previously Untreated Multiple Myeloma.

Introduction: Orlowski et al were the first to report that addition of PLD resulted in enhanced efficacy of bortezomib. To further optimize the clinical efficacy of these agents we included thalidomide to the regimen. In a previous report we described the clinical efficacy of this novel, non-steroidal regimen that incorporated bortezomib (V), pegylated liposomal doxorubicin (D) and thalidomide (T) in patients with relapsed or refractory multiple myeloma (MM). High clinical responses in heavily pretreated patients, even in the absence of steroids encouraged us to investigate this regimen in previously untreated MM patients. Here we report for the first time the efficacy and toxicity profile of the VDT regimen in treatment naïve MM patients enrolled on a phase II clinical study at our center.

METHOD: All previously untreated MM patients were eligible for this study. Bortezomib (1.3mg/m²) was given on days 1, 4, 15, and 18, pegylated liposomal doxorubicin was given (20mg/m²) on days 1 and 15 and thalidomide (200mg) was given everyday continuously throughout the treatment. Patients received treatment on a 4-week cycle. Acyclovir 400mg PO BID and low-dose warfarin was given for prophylaxis of herpes zoster and venous thromboembolism respectively.

RESULTS: A total of 26 patients (median age-- 60 range 40–82 years), 16 M and 10 F have so far been enrolled. Advance stage III disease was noted in ---of the patients. The median beta 2 microglobulin was 4 (range1.6–9.7), albumin of 4 (range 3.1–4.8) and LDH was 333 (range 152–1057). Patients received a median of 5 treatment cycles (range 1–8). Toxicity: The most common grade 3 or 4 hematologic toxicities included lymphopenia (27%) and neutropenia (15%), while the non-hematologic toxicity included infections 15% (n=4 patients). The incidence of grade 3 or 4 plantar palmar erythrodysthesia was 4% (n=1). Venous thromboembolism was not observed in any patient to date. Response: To date 17 patients are available for response assessment (EBMT criteria?), 7 patients are too early for response assessment. The ORR of this regimen is 65% with IFE negative CR observed in 3 patients (17.6%). Another 5 patients achieved a stable disease with only 1 progressive disease observed on the regimen so far.

Conclusion: VDT is a novel non-steroidal regimen with clinical efficacy in previously untreated myeloma patients. Overall toxicity is manageable. Several patients remain on treatment and currently not evaluable for response. Detailed and updated results of this study will be presented at the meeting.