Successful mobilization of PBSCs predicts favorable outcomes in multiple myeloma patients treated with novel agents and autologous transplantation

Abstract

Incorporation of novel agents into auto-SCT for patients with multiple myeloma has led to improvement in their outcomes. However, the effects of new drugs, either single or combined, on PBSC mobilization have not been fully evaluated, particularly in phase 3 clinical studies. We analyzed the impact of two novel agent-based induction treatments in patients enrolled in the GIMEMA MMY-3006 study comparing bortezomib, thalidomide and dexamethasone (VTD) versus thalidomide and dexamethasone (TD) in preparation for double auto-SCT. Results showed that a short-term induction therapy with VTD did not adversely affect CD34+ cell yields as compared with TD (9.75 vs 10.76 × 10 6 CD34 + cells/kg, P = 0.220). For poor mobilizers (o4 × 10 6 CD34 + cells/kg), 5-year rates of time to progression (TTP), progression-free survival (PFS) and overall survival (OS) were significantly shorter than for successful mobilizers (TTP:17 vs 48%, P o0.0001; PFS: 16 vs 46%, P o 0.0001; OS: 50 vs 80%, P o 0.0001). These differences were retained across patients randomized to the TD arm; conversely, no differences in outcomes were seen in patients treated with VTD, irrespective of the number of harvested CD34 + cells. The number of collected PBSCs predicted better outcomes after auto-SCT and VTD overcame the negative impact of a poor stem cell mobilization.

Poor peripheral blood stem cell mobilization affects long‐term outcomes in multiple myeloma patients undergoing autologous stem cell transplantation

“…Importantly, this work validates the findings from the phase 3, open‐label, multicenter GIMEMA MMY‐3006 (NCT01134484) study published in 2015. This trial assessed the efficacy and safety of VTD versus TD induction therapy prior to ASCT and reported that poor mobilizers experienced inferior outcomes, defined as 5‐year rates of time to progression (TTP), PFS, and OS, relative to those that readily mobilized PBSCs …”

“…This trial assessed the efficacy and safety of VTD versus TD induction therapy prior to ASCT and reported that poor mobilizers experienced inferior outcomes, defined as 5-year rates of time to progression (TTP), PFS, and OS, relative to those that readily mobilized PBSCs. 24 Although retrospective, our analysis has few positive aspects that is usually lacking in prospective studies. Because our dataset includes patients that were followed at our institution over a 10-year period, we were able to capture a wide range of induction regimens and salvage therapies, as well as their impact on PBSC mobilization.…”

“…In patients with MM, the GIMEMA MMY‐3006 trial evaluated outcomes of patients treated with bortezomib, thalidomide, dexamethasone (VTD) versus thalidomide and dexamethasone (TD), followed by cyclophosphamide (4 g/m 2 ) and granulocyte colony stimulating factor (G‐CSF) 10 mcg/kg/day for PBSC mobilization. Patients in this study that failed to reach the collection target went on to experience an inferior time to disease progression, PFS, and OS …”

“…Patients in this study that failed to reach the collection target went on to experience an inferior time to disease progression, PFS, and OS. 24 The introduction and acceptance of the CXCR4 antagonist plerixafor has reduced the number of poor mobilizers and the incidence of mobilization failures. In a multicenter, double-blinded, placebo-controlled phase 3 study, a significantly higher percentage of MM patients treated with G-CSF plus plerixafor met the primary endpoint of collecting 6 3 10 6 CD341 cells/kg with 2 apheresis attempts (71.6% vs 34.4%).…”

Multiple myeloma: New surface antigens for the characterization of plasma cells in the era of novel agents

“…In Western countries the number of new cases of MM is 5.9 per 100,000 people per year and the median age at diagnosis is 69 years . MM is still an incurable disease and novel therapeutic drugs are required to treat patients . Monoclonal antibodies (mAbs) may improve MM treatment, similarly to other haematological malignancies.…”