The Medical Research Council (MRC) Myeloma IX study evaluated the role of the addition of thalidomide to induction and maintenance therapy, ran from May 2003 – November 2007, randomising 1,970 patients, and now has a median follow-up (FU) of 6 years, giving it improved power to detect clinically relevant changes. The trial comprised 2 patient pathways, which were not determined by strict age cut-off; one for younger fitter patients (intensive pathway), comparing CTD (cyclophosphamide, thalidomide, dexamethasone) (n=555 evaluable) with CVAD (cyclophosphamide, vincristine, adriamycin, dexamethasone) (n=556), all patients being planned to receive ASCT. The other pathway, for older, less fit patients (non-intensive pathway) compared MP (melphalan and prednisolone) (n=423) with an attenuated CTD (CTDa) (n=426). In both pathways, following initial treatment, patients were randomised to low-dose thalidomide or no maintenance until progression (n=820). Primary endpoints were response rate, progression free survival (PFS) and overall survival (OS). Adverse FISH groups were defined as any of t(4;14), t(14;16), t(14;20), 1q+, 17p−, or 1p32− (in the intensive pathway only); the remainder being defined as standard risk.
We have previously presented data from the study with a median FU of 3.7 years, where there appeared to be emergent survival benefits for thalidomide induction, though not reaching significance. The 6 year median FU OS analysis provides us with the ability to analyze the impact of these regimens on the long-term survival of this group of patients. This late analysis is important, as while early FU is more sensitive to the impact of treatments on higher-risk disease, longer term FU is more sensitive to the impact of therapies on standard-risk disease, where thalidomide may exert its most important effects. The results of this late analysis at a median of 6 years will inform our use of thalidomide based on FISH risk status. The same arguments apply to the use of thalidomide maintenance on high- and standard-risk disease defined by FISH, where the early analysis showed significantly improved PFS with a hint of improved OS in the standard-risk group, whereas there was no impact on PFS for high-risk disease with significantly impaired OS. The results of this long-term analysis will allow us to further analyse the potential for an emergent OS benefit for thalidomide maintenance in the standard-risk disease group.
In conclusion, we will present the late analysis of this important study, which will specifically inform how the use of thalidomide as induction and maintenance can impact on OS in standard-risk disease defined by FISH.