Partial Response at Completion of Bortezomib-Thalidomide-Dexamethasone (VTd) Induction Regimen Upfront in Multiple Myeloma Does Not Preclude Response to VTd in Consolidation

The impact of consolidation on response rates and PFS has recently been demonstrated after induction and autotransplantation upfront in Multiple Myeloma (MM). We further showed that patients in ≥VGPR following the intensification procedure benefited most from consolidation. Question remains as to the benefit of consolidation for patients in PR at completion of induction - feature of partial resistance to the induction regimen. We collected data from 54 newly diagnosed MM treated with VTd-auto-VTd regimen that reached only PR at completion of the induction procedure. Overall, 37 patients (68%) improved depth of response (≥VGPR) at completion of consolidation, including 35% that reached CR and 38% solely related to consolidation. Of patients that remained on PR or improved depth of response after ASCT, 26% and 38% further responded to consolidation, respectively. With a median follow-up of 36 months, improved depth of response translated into lower relapse rate compared with patients remaining in PR, 19% vs. 36%. This difference was more striking in patients that reached CR vs. others, 8% and 38%, respectively (p=0.039). The median TTP was prolonged in patients that improved depth of response after consolidation (p=0.012), with a 3-year TTP of 87% vs. 18% otherwise. In multivariate analysis, lack of improved depth of response to consolidation independently predicted shorten median TTP [OR=4.4, 95%CI=1-21; p=0.039], with elevated LDH and beta2m, and adverse FISH. This study shows that VTd consolidation should be recommended to patients solely on PR at completion of induction with VTd, feature of lower sensitivity to VTd.

[1]  B. Pégourié,et al.  Consolidation with VTd significantly improves the complete remission rate and time to progression following VTd induction and single autologous stem cell transplantation in multiple myeloma , 2013, Leukemia.

[2]  M. Kersten,et al.  Bortezomib induction and maintenance treatment in patients with newly diagnosed multiple myeloma: results of the randomized phase III HOVON-65/ GMMG-HD4 trial. , 2012, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[3]  M. Boccadoro,et al.  Bortezomib-thalidomide-dexamethasone is superior to thalidomide-dexamethasone as consolidation therapy after autologous hematopoietic stem cell transplantation in patients with newly diagnosed multiple myeloma. , 2012, Blood.

[4]  B. Pégourié,et al.  Lenalidomide maintenance after stem-cell transplantation for multiple myeloma. , 2012, The New England journal of medicine.

[5]  M. Beksac,et al.  IMWG consensus on maintenance therapy in multiple myeloma. , 2012, Blood.

[6]  M. Dimopoulos,et al.  International Myeloma Working Group consensus approach to the treatment of multiple myeloma patients who are candidates for autologous stem cell transplantation. , 2011, Blood.

[7]  P. Moreau,et al.  Current trends in autologous stem-cell transplantation for myeloma in the era of novel therapies. , 2011, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[8]  D. Esseltine,et al.  Achievement of VGPR to induction therapy is an important prognostic factor for longer PFS in the IFM 2005-01 trial. , 2011, Blood.

[9]  A. Chanan-Khan,et al.  Importance of achieving a complete response in multiple myeloma, and the impact of novel agents. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[10]  M. Boccadoro,et al.  Major tumor shrinking and persistent molecular remissions after consolidation with bortezomib, thalidomide, and dexamethasone in patients with autografted myeloma. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[11]  P. Moreau,et al.  Achievement of at least very good partial response is a simple and robust prognostic factor in patients with multiple myeloma treated with high-dose therapy: long-term analysis of the IFM 99-02 and 99-04 Trials. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[12]  R A Kyle,et al.  Criteria for diagnosis, staging, risk stratification and response assessment of multiple myeloma , 2009, Leukemia.

[13]  N. Munshi,et al.  High-dose therapy with single autologous transplantation versus chemotherapy for newly diagnosed multiple myeloma: A systematic review and meta-analysis of randomized controlled trials. , 2007, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[14]  J. Rossi,et al.  A Prospective, Randomized Trial of Autologous Bone Marrow Transplantation and Chemotherapy in Multiple Myeloma , 1996 .

[15]  J. Rossi,et al.  A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. Intergroupe Français du Myélome. , 1996, The New England journal of medicine.