Recent understanding of MM biology suggests that MM cells rely on their microenvironment for disease progression and dissemination. MM cell interaction with stromal cells in the bone marrow microenvironment fosters chemotherapy resistance. Targeting the microenvironment with novel biologic agents such as thalidomide (T) has shown encouraging clinical results in patients with previously untreated as well as relapsed/refractory MM. We have previously shown here that VAD plus low dose T (t) is an effective salvage regimen for VAD refractory pts. We report the preliminary results of an ongoing phase II trial studying a combined chemoimmunotherapeutic approach - standard VAD plus t (200 mg) in treatment-naïve MM pts. This regimen was designed to target concurrently the malignant cell and its microenvironment. MM pts, ≥ Stage I with no prior therapy were eligible for study. Monthly infusional VAD (standard dose) was given for 4 cycles every 28 days concurrently with t for 4 months. t (100mg) was started 1 wk prior to VAD and was escalated in 1–2 wks to 200mg. Pts were evaluated for response after each cycle and after cycle 4 using SWOG criteria. Pts characteristics include: enrolled n=16, 8M, 8F; median age 58 yrs range 46–77; Stage III disease n=11, Stage II, n=3 and Stage 1, n=1; and Median B2M, 1.9 mg/L (range 1.2–11.5). Low dose coumadin (1–2 mg) was used for venous thromboembolism (VTE) prophylaxis, t was also held during the 4 days of each infusion of VAD. All pts are evaluable for toxicity and 11 are evaluable for response after completing 4 cyc. 10/11 (91%) responded clinically; CR, n=3, PR, n=7. One pt had progressive disease. Three pts with responding disease were removed from study for Grade III toxicity (1 adriamycin associated cardiomyopathy, 1 pulmonary hypertension and 1 recurrent infections) but are not included in response evaluation. Toxicities: fatigue (Gr. II) was the most common side effect (25%) and DVT was noted in 2 (12%). All pts eligible for stem cell (SC) transplant (n=7), were able to collect adequate amount of SC post VAD-t. Preliminary results of this study suggest that VAD-t is an effective and well-tolerated regimen with improved ORR compared to standard VAD regimen in pts with treatment naïve MM. No increase in incidence of VTE was noted with the combination. Adequate SC collection was achieved in transplant eligible pts. Accrual is ongoing on this study and updated results will be presented at the annual meeting.

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