Complete remission sustained 3 years from treatment initiation is a powerful surrogate for extended survival in multiple myeloma

BACKGROUND. Complete response (CR) has been considered a necessary although not sufficient early clinical endpoint for extended survival in multiple myeloma. METHODS. By using Total Therapy 2 (TT2) clinical outcome data in 668 patients, whether sustained CR (SUS‐CR) was potentially a superior surrogate for survival than attaining CR status per se was evaluated. RESULTS. Compared with not achieving CR (NON‐CR) and especially achieving and subsequently losing CR status (LOS‐CR) within a 3‐year landmark from treatment initiation, SUS‐CR was associated with highly superior postlandmark survival ( P < .0001). These results were validated in 231 untreated patients enrolled in the predecessor trial, TT1 (hazard ratio [HR] = 0.54, P = .013) and in 1103 previously treated patients on other transplant protocols (HR = 0.49; P < .001). CONCLUSIONS. In all 3 trial settings the survival benefit of SUS‐CR was independent of metaphase abnormalities as a dominant adverse parameter. Given its bleak prognosis despite high CR rates, SUS‐CR should be evaluated as a primary trial endpoint in high‐risk myeloma. Cancer 2008. © 2008 American Cancer Society.