[Multiple myeloma: Maintenance therapy after autologous hematopoietic stem cell transplantation, depending on minimal residual disease].

AIM To determine the efficiency of maintenance therapy with bortezomib in patients with multiple myeloma (MM) who have achieved complete remission (CR) after autologous hematopoietic stem cell (auto-HSCT), depending on the presence of minimal residual disease (MRD). SUBJECTS AND METHODS In January 2014 to February 2016, fifty-two MM patients (19 men and 33 women) aged 24 to 66 years (median 54 years), who had achieved CR after auto-HSCT, were randomized to perform maintenance therapy with bortezomib during a year. On day 100 after auto-HSCT, all the patients underwent immunophenotyping of bone marrow plasma cells by 6-color flow cytometry to detect MRD. Relapse-free survival (RFS) was chosen as a criterion for evaluating the efficiency of maintenance therapy. RESULTS After auto-HSCT, MRD-negative patients had a statistically significantly higher 2-year RFS rate than MRD-positive patients: 52.9% (95% confidence interval (CI), 35.5 to 70.5%) versus 37.2% (95% CI, 25.4 to 49.3%) (p=0.05). The presence of MRD statistically significantly increased the risk of relapse (odds ratio 1.7; 95% CI, 1.2 to 3.4; p=0.05). Two-year cumulative risk of relapse (using the Kaplan-Meier) after auto-HSCT did not statistically significantly differ in MRD-negative patients receiving (n=15) and not receiving (n=10) maintenance therapy with bortezomib (p=0.58). After completion of maintenance treatment, 42% of the MRD-positive patients achieved a negative status. In the MRD-positive patients who had received maintenance therapy, the average time to recurrence was 5 months longer than that in the naïve patients: 17.3 versus 12.3 months. CONCLUSION The MRD status determined in MM patients who have achieved CR after auto-HSCT is an important factor for deciding on the use of maintenance therapy.

[1]  L. Mendeleeva,et al.  Maintenance Therapy after Autologous Haematopoietic Stem Cell Transplantation (auto-HSCT) in Multiple Myeloma Patients with and without Minimal Residual Disease (MRD) , 2016 .

[2]  S. Rajkumar,et al.  Updated Diagnostic Criteria and Staging System for Multiple Myeloma. , 2016, American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting.

[3]  A. Órfão,et al.  Consensus guidelines for myeloma minimal residual disease sample staining and data acquisition , 2016, Cytometry. Part B, Clinical cytometry.

[4]  D. Dingli,et al.  Importance of achieving stringent complete response after autologous stem-cell transplantation in multiple myeloma. , 2013, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[5]  U. Mellqvist,et al.  Bortezomib consolidation after autologous stem cell transplantation in multiple myeloma: a Nordic Myeloma Study Group randomized phase 3 trial. , 2013, Blood.

[6]  A. Oriol,et al.  Superiority of bortezomib, thalidomide, and dexamethasone (VTD) as induction pretransplantation therapy in multiple myeloma: a randomized phase 3 PETHEMA/GEM study. , 2012, Blood.

[7]  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.

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

[9]  D. Esseltine,et al.  Superior outcomes associated with complete response in newly diagnosed multiple myeloma patients treated with nonintensive therapy: analysis of the phase 3 VISTA study of bortezomib plus melphalan-prednisone versus melphalan-prednisone. , 2010, Blood.

[10]  S. Lonial,et al.  The Importance of Complete Response in Outcomes in Myeloma , 2009, Cancer Journal.

[11]  L. Escoda,et al.  Influence of pre- and post-transplantation responses on outcome of patients with multiple myeloma: sequential improvement of response and achievement of complete response are associated with longer survival. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[12]  A. Órfão,et al.  Multiparameter flow cytometric remission is the most relevant prognostic factor for multiple myeloma patients who undergo autologous stem cell transplantation. , 2008, Blood.

[13]  P. Richardson,et al.  Clinically relevant end points and new drug approvals for myeloma , 2008, Leukemia.

[14]  Jason McCoy,et al.  Standard chemotherapy compared with high-dose chemoradiotherapy for multiple myeloma: final results of phase III US Intergroup Trial S9321. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[15]  P. Ravaud,et al.  High-dose therapy and autologous blood stem-cell transplantation compared with conventional treatment in myeloma patients aged 55 to 65 years: long-term results of a randomized control trial from the Group Myelome-Autogreffe. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[16]  R. Bataille,et al.  Single versus double autologous stem-cell transplantation for multiple myeloma. , 2003, The New England journal of medicine.

[17]  M. Dimopoulos,et al.  Randomized trial of α‐interferon or dexamethasone as maintenance treatment for multiple myeloma , 2000 .

[18]  M. Gore,et al.  A randomized trial of maintenance interferon following high‐dose chemotherapy in multiple myeloma: long‐term follow‐up results , 1998, British journal of haematology.

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