Details

Autor(en) / Beteiligte

• 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

Titel

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

Ist Teil von

• Journal of clinical oncology, 2010-04, Vol.28 (12), p.2077-2084

Ort / Verlag

United States: American Society of Clinical Oncology

Erscheinungsjahr

2010

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.