Author(s): F. Van Rhee, B. Barlogie, J. Szymonifka, E. J. Anaissie, B. P. Nair, S. Waheed, Y. Alsayed, N. Petty, J. D. Shaughnessy, A. Hoering, J. Crowley
Background: The role of maintenance therapy in the management of multiple myeloma remains unclear.
Methods: TT3 applied 3 years of maintenance therapy with VTD in year 1 and TD in years 2 and 3. The impact was examined on overall survival (OS), event-free survival (EFS) and complete response (CR) incidence and its duration (CRD), and post-relapse survival (PRS) of cumulative doses of V, T and D, employing time-dependence methodology in Cox regression models relevant to induction, peri-transplantation, consolidation and maintenance.
Results: Univariately, OS and EFS were longer with higher doses of all agents during induction, consolidation (except T) and maintenance (except V, T); CR rates were higher with V, T and D dosing during most phases; CRD was not affected by VTD dosing; PRS was longer with higher total V dosing and not compromised by T and D dosing prior to relapse. The independent favorable OS/EFS impact of D induction dosing provided the rationale for examining the expression of glucocorticoid receptor NR3C1, top-tertile levels of which significantly prolonged OS and EFS and rendered outcomes independent of D and T dosing, while T and D but not V dosing were critical to outcome improvement in the low-tertile NR3C1 setting.
Conclusions: The absence of adverse effects on PRS of any of the VTD components with a benefit from V supports the use up-front of all active agents in a dose- dense and dose-intense fashion, as practiced in TT3, toward maximizing myeloma survival. The observation of NR3C1 top tertile levels being associated with superior and lower tertile levels with inferior survival outcomes support IFM data on the beneficial effect of amp5q31.3 where NR3C1 maps.