Thalidomide plus dexamethasone as a maintenance therapy after autologous hematopoietic stem cell transplantation improves progression‐free survival in multiple myeloma

Abstract

Despite the good response of stem cell transplant (SCT) in the treatment of multiple myeloma (MM), most patients relapse or do not achieve complete remission, suggesting that additional treatment is needed. We assessed the impact of thalidomide in maintenance after SCT in untreated patients with MM. A hundred and eight patients (<70 years old) were randomized to receive maintenance with dexamethasone (arm A; n 5 52) or dexamethasone with thalidomide (arm B; n 5 56; 200 mg daily) for 12 months or until disease progression. After a median follow-up of 27 months, an intention to treat analysis showed a 2-year progression-free survival (PFS) of 30% in arm A (95% CI 22-38) and 64% in arm B (95% CI 57-71; P 5 0.002), with median PFS of 19 months and 36 months, respectively. In patients who did not achieve at least a very good partial response, the PFS at 2 years was significantly higher when in use of thalidomide (19 vs. 59%; P 5 0.002). Overall survival at 2 years was not significantly improved (70 vs. 85% in arm A and arm B, respectively; P 5 0.27). The addition of thalidomide to dexamethasone as maintenance improved the PFS mainly in patients who did not respond to treatment after SCT. Am. J. Hematol. 87:948-952, 2012. V

Augmenting Autologous Stem Cell Transplantation to Improve Outcomes in Myeloma

“…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).…”

“…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.…”

Maintenance Therapy for Multiple Myeloma

“…There was no difference in the 3-year OS: 80% for the thalidomide and dexamethasone arm and 81% for the observation group (P=0.82). A Brazilian study studied 108 MM patients receiving single AHSCT by randomizing them to 12 months of either thalidomide and dexamethasone or dexamethasone alone maintenance 51 . The 2-year PFS was 64% for the thalidomide and dexamethasone arm and 30% for the dexamethasone only arm (P=0.002).…”

“…For patients with high risk cytogenetic analyses, the OS was inferior for patients receiving thalidomide maintenance when compared to no maintenance (35 versus 47 months, P=0.01). There have been four studies that have examined thalidomide plus glucocorticoids as maintenance after AHSCT [49][50][51][52] . An Australian study compared 243 patients receiving one year of thalidomide with prednisolone until progression to patients receiving prednisolone alone until progression 49 .…”

The Role of Pre-Transplant Induction Regimens and Autologous Stem Cell Transplantation in the Era of Novel Targeted Agents

“…In one study, maintenance with prednisone every other day improved PFS and OS, (38) yet, in another study, no benefit was seen with single agent dexamethasone. (39) Data are therefore insufficient to recommend corticosteroids maintenance therapy.In six different randomized trials, thalidomide maintenance was used post-ASCT: thalidomidebased maintenance arm was compared with alpha-interferon, dexamethasone, pamidronate, prednisone, or observation in the different trials (19,35,(42)(43)(44)(45). A recent meta-analysis showed a reduced risk of progression (HR 0.64, P<0.001) and death (HR 73, P=0.002) with thalidomide maintenance (46).…”