The issue of curability for multiple myeloma, debated with enthusiasm by some, has been challenged by others preferring to pursue the objective of chronic disease control over disease eradication. While the issue of curability is compounded by significant co-morbidity issues in the elderly myeloma patient, we have recently reported that Kaplan-Meier plots of complete remission duration (CRD) , event-free survival (EFS), and overall survival (OS) are compatible with cure models in our Total Therapy (TT) programs (1). These cure models assume that a fraction of patients have long-term remission duration, EFS, or OS, while the remainder fail at a constant rate. Kaplan-Meier plots for OS and EFS as well as CRD are depicted in Figure 1A for TT1, TT2, and TT3 protocols. EFS curves demonstrating significant cure fraction estimates for TT1, TT2 (both control and experimental arms), and TT3 are depicted in Figure 1B; in TT3, a significant cure fraction estimate was limited to gene expression profiling-defined low-risk myeloma. Cure fraction estimates are jointly depicted for all 3 TT protocols in Figure 1C, along with significance comparisons among the protocols.
Figure 1. Modeling Cure Fractions (CF) from event-free survival (EFS) plots
A: Kaplan-Meier estimates for overall survival (OS), event-free survival (EFS), and complete response duration (CRD) for Total Therapy protocols TT1, TT2 without and with thalidomide, and TT3.
B: Significant CF’s are projected for all three TT protocols as evident from superimposed actual EFS (solid lines) and model-based estimates (dotted lines); in TT3, a significant CF is limited to gene expression profiling-defined low-risk myeloma, based on a 70-gene model (GEP-70).
C: Summary of CF data in all 3 protocols, revealing a striking advance in TT3 over TT2+Thal.
- Barlogie B, Shaugnessy JD, Anaissie E, et al. Modeling for Cure with Total Therapy (TT) Trials for Newly Diagnosed Multiple Myeloma (MM): Let the Math Speak. ASH 2009 114:744.