Maurizio Zangari, Bart Barlogie, Joth Jacobson, Erik Rasmussen, Michael Burns, Bob Kordsmeier, John D. Shaughnessy, Elias J. Anaissie, Raymond Thertulien, Athanasios Fassas, Choon-Kee Lee, David Schenkein, Jerome B. Zeldis, Guido Tricot Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR, USA; Cancer Research And Biostatistics, Seattle, WA, USA; Millennium Pharmaceutical Company, Cambridge, MA, USA; Celgene Corporation, Warren, NJ, USA

A phase I/II trial was initiated to determine whether the synergy observed in pre-clinical studies between V + T could be confirmed clinically and to investigate the cumulative, especially neurologic, toxicities. The VTD regimen applied V at a dose of 1 mg/m² on days 1, 4, 8 and 11 and added T at dose increments per ≥ 10 patients of 50, 100, 150 and 200 mg (in the absence of > grade 2 neurotoxicity). A second cohort was then started at V 1.3 mg/m² on days on 1, 4, 8 and 11 with addition of T in the same incremental dosing schedule as with V at 1.0 mg/m²; DEX was added as early as with cycle #4 if partial response (PR) was not achieved. PR was defined as ≥ 50% reduction in serum M protein or ≥ 75% reduction of urine M protein. A total of 56 patients have been enrolled (V 1.0 mg/m² + T 50 mg, n=12; T 100 mg, n=10; T 150 mg, n=11; T 200 mg, n=13; V 1.3 mg/m² + T 50 mg, n=10). Patient characteristics included prior autotransplants in all 56 patients, tandem transplants in 72%; prior thalidomide exposure and resistance in 78%; more than 5 years of prior therapy in 37%, abnormal cytogenetics (CA) in 76% including del 13 in 52%. Cumulative incidence of response according to different levels of M protein reduction (MPR) are depicted, reaching levels of 70% for MPR of >=25% and 53% for MPR of >=50% (after 4 cycles) and 22% CR + n-CR after 8 cycles.

Responses occurred independently of CA and of V and T doses. Cumulative grade > 2 neurotoxicity was not observed during the first 4 cycles of therapy. 12 month estimates of EFS and OS were significantly higher in the 14 patients without CA compared to the 41 patients exhibiting CA.

Collectively, our data indicate excellent tolerance and activity of the VTD regimen in a very high risk patient population. VTD deserves evaluation in MM patients earlier in their disease.
Abstract #830 appears in Blood, Volume 102, issue 11, November 16, 2003
Keywords: Myeloma|Velcade|Thalidomide