Background: A phase II trial of Thal/Dex combination and Thai as first line therapy in new untreated MM with laboratory correlative studies (interim analysis). Methods: Patients (pts) with active MM were treated with the Thal/Dex combination. Pts with smoldering or indolent MM (SMM/IMM) were treated with Thai alone. Thai was given orally at a dose of 200 mg/day for 2 weeks, and then increased as tolerated by 200 mg/day every 2 weeks to a maximum dose of 800 mg/day. Dex was given orally at a dose of 40 mg/day orally on days 1-4, 9-12, 17-20 (odd cycles) and 40 mg/day days 1-4 (even cycles) repeated monthly. Response was defined as a decrease in serum and urine monoclonal (M) protein by 50% or greater. Bone marrow (BM) microvessel density (MVD) using immunostaining for CD34 was estimated by determining the average number of vessels in 3 hot spots at 400x magnification. BM angiogenesis was also visually graded as low, intermediate and high. Results: 42 pts (26 with active MM and 16 with smoldering/indolent MM) were studied. In the Thal/Dex arm, 2 pts had grade 3-4 skin toxicity among the first 7 pts treated, at Thai dose of 400mg. The Thal/Dex arm was then amended to stop dose escalation, and keep Thai dose constant at 200mg. An objective response was seen in 20 pts (77%) with active MM treated with Thal/Dex. The response rate was 86% with Thai dose escalation (6 of 7 pts), and 74% with Thai dose constant at 200mg (14 of 19 pts). Major grade 3-4 toxicities were rash in 3 pts, and sedation, constipation and myalgias in 1 pt each. In the SMM/IMM arm, 6 pts (38%) achieved a response with Thai alone. Median pre-treatment MVD was 27 in the active MM arm, and 7 in the SMM/IMM arm (p<0.001). Angiogenesis grade was high in 64% of active MM and 8% of SMM/IMM, (p<0.001). The proportion of pts with a high(l) PCLI was 67%, 9%, 0% for high, intermediate, and low grade angiogenesis respectively (p<0.001 ). No significant changes were observed in MVD following treatment; pre-treatment MVD and angiogenesis grade did not appear to be associated with response to therapy. Conclusions: Thal/Dex is strikingly effective as first line therapy (and an oral alternative to infusional VAD) for new, active MM. SMM/IMM pts also appear to achieve significant responses with Thai alone. However, these results are preliminary and responses/toxicities are still being evaluated and need further confirmation in the final analysis of this trial.
|Original language||English (US)|
|Issue number||11 PART I|
|State||Published - Dec 1 2000|
ASJC Scopus subject areas
- Cell Biology