A randomized phase 3 trial of thalidomide and prednisone as maintenance therapy after ASCT in patients with MM with a quality-of-life assessment: the National Cancer Institute of Canada Clinicals Trials Group Myeloma 10 Trial

Abstract

• Thalidomide and prednisone maintenance after transplantation improves progressionfree but not overall survival.We conducted a randomized, controlled trial comparing thalidomide-prednisone as maintenance therapy with observation in 332 patients who had undergone autologous stem cell transplantation with melphalan 200 mg/m 2 . The primary end point was overall survival (OS); secondary end points were myeloma-specific progression-free survival, progression-free survival, incidence of venous thromboembolism, and health-related quality of life (HRQoL). With a median follow-up of 4.1 years, no differences in OS between thalidomide-prednisone and observation were detected (respective 4-year estimates of 68% vs 60%, respectively; hazard ratio ‫؍‬ 0.77; P ‫؍‬ .18); thalidomide-prednisone was associated with superior myeloma-specific progression-free survival and progression-free survival (for both outcomes, the 4-year estimates were 32% vs 14%; hazard ratio ‫؍‬ 0.56; P < .0001) and more frequent venous thromboembolism (7.3% vs none; P ‫؍‬ .0004). Median survival after first disease recurrence was 27.7 months with thalidomide-prednisone and 34.1 months in the observation group. Nine second malignancies were observed with thalidomide-prednisone versus 6 in the observation group. Those allocated to thalidomideprednisone reported worse HRQoL with respect to cognitive function, dyspnea, constipation, thirst, leg swelling, numbness, dry mouth, and balance problems. We conclude that maintenance therapy with thalidomide-prednisone after autologous stem cell transplantation improves the duration of disease control, but is associated with worsening of patient-reported HRQoL and no detectable OS benefit. (Blood. 2013;121(9):1517-1523)

Chemotherapy plus lenalidomide versus autologous transplantation, followed by lenalidomide plus prednisone versus lenalidomide maintenance, in patients with multiple myeloma: a randomised, multicentre, phase 3 trial

“…19 Maintenance with thalidomide-prednisone prolonged PFS, with conflicting OS results. 20,21 This study aims to compare the efficacy and safety of consolidation with CRD versus MEL200-ASCT, followed by maintenance with lenalidomide-prednisone versus lenalidomide alone, in NDMM patients eligible for transplantation.…”

Augmenting Autologous Stem Cell Transplantation to Improve Outcomes in Myeloma

“…Complete response rate has historically correlated poorly with overall survival (Baldini 1991;Riccardi et al, 2003;Durie et al, 2004), and clearly does not take account of quality of life aspects, which are affected by increasingly prolonged myeloma therapy regimens. In early trials, time to progression did correlate with overall survival, but with consolidation treatment this association is no longer seen (Alexanian et al, 2000;Attal et al, 2012;Maiolino et al, 2012;Sonneveld et al, 2012;Stewart et al, 2013). PFS2, the time from first treatment to second relapse, takes account of tumour resistance induced by the first line of treatment, and to date studies have shown it is prolonged in association with PFS (Palumbo et al, 2014b;Tacchetti et al, 2014), but it has not yet been validated as a surrogate for OS, and still takes years of follow up to report mature data.…”

“…A smaller RCT of similar design found a non-significant trend towards increased survival in the thalidomide arm (Maiolino et al, 2012). However an RCT of thalidomide plus prednisolone versus no maintenance found no overall survival difference, and highlighted worse quality of life scores in the maintenance group (Stewart et al, 2013). In all of these trials, adverse events of grade 3 or 4 were much more common in the thalidomide arm, and this is reflected in a thalidomide discontinuation rate of 30% within a year in the study by Spencer et al…”

Consolidation and maintenance therapy for multiple myeloma after autologous transplantation: where do we stand?

“…To date, only a few studies have analyzed the impact of consolidation or maintenance therapy on QoL. Stewart et al 41 found that the application of thalidomide and prednisone following ASCT had a substantial impact on QoL. Patients reported worse QoL with respect to cognitive function, dyspnea, constipation, thirst, leg swelling, numbness, dry mouth and balance problems.…”