Major Tumor Shrinking and Persistent Molecular Remissions After Consolidation With Bortezomib, Thalidomide, and Dexamethasone in Patients With Autografted Myeloma

作者:Ladetto Marco*; Pagliano Gloria; Ferrero Simone; Cavallo Federica; Drandi Daniela; Santo Loredana; Crippa Claudia; De Rosa Luca; Pregno Patrizia; Grasso Mariella; Liberati Anna Marina; Caravita Tommaso; Pisani Francesco; Guglielmelli Tommasina; Callea Vincenzo; Musto Pellegrino; Cangialosi Clotilde; Passera Roberto; Boccadoro Mario; Palumbo Antonio
来源:Journal of Clinical Oncology, 2010, 28(12): 2077-2084.
DOI:10.1200/JCO.2009.23.7172

摘要

Purpose
We investigated the effect on minimal residual disease, by qualitative and real-time quantitative polymerase chain reaction (RQ-PCR), of a consolidation regimen that included bortezomib, thalidomide, and dexamethasone (VTD) in patients with multiple myeloma (MM) responding to autologous stem-cell transplantation (auto-SCT).
Patients and Methods
Patients achieving at least very good partial response who had an available molecular marker based on the immunoglobulin heavy-chain rearrangement received four courses of treatment every month: four infusions per month of bortezomib at 1.6 mg/m(2), thalidomide at 200 mg/d, and dexamethasone at 20 mg/d on days 1 to 4, 8 to 11, and 15 to 18. Patients were studied with tumor-clone-specific primers by qualitative nested PCR and RQ-PCR.
Results
Of 39 patients enrolled, 31 received the four VTD courses. Immunofixation complete responses increased from 15% after auto-SCT to 49% after VTD. Molecular remissions (MRs) were 3% after auto-SCT and 18% after VTD. Median time to maximum response was 3.5 months. So far, no patient in MR has relapsed (median follow-up, 42 months). VTD consolidation induced an additional depletion of 4.14 natural logarithms of tumor burden by RQ-PCR. Patients with a tumor load less than the median value after VTD had outcomes better than those who had tumor loads above the median value after VTD (at median follow-up: progression-free survival, 100% v 57%; P < .001).
Conclusion
To the best of our knowledge, this study is the first to document the occurrence of persistent MRs in a proportion of MM patients treated without allogeneic transplantation. Moreover, the major reduction in tumor load recorded by RQ-PCR after VTD suggests that unprecedented levels of tumor cell reduction can be achieved in MM thanks to the new nonchemotherapeutic drugs. J Clin Oncol 28: 2077-2084.

  • 出版日期2010-4-20