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.
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.
Authors: Michele Cavo; S Vincent Rajkumar; Antonio Palumbo; Philippe Moreau; Robert Orlowski; Joan Bladé; Orhan Sezer; Heinz Ludwig; Meletios A Dimopoulos; Michel Attal; Pieter Sonneveld; Mario Boccadoro; Kenneth C Anderson; Paul G Richardson; William Bensinger; Hans E Johnsen; Nicolaus Kroeger; Gösta Gahrton; P Leif Bergsagel; David H Vesole; Hermann Einsele; Sundar Jagannath; Ruben Niesvizky; Brian G M Durie; Jesus San Miguel; Sagar Lonial Journal: Blood Date: 2011-03-29 Impact factor: 22.113
Authors: Antje Hoering; John Crowley; John D Shaughnessy; Klaus Hollmig; Yazan Alsayed; Jackie Szymonifka; Sarah Waheed; Bijay Nair; Frits van Rhee; Elias Anaissie; Bart Barlogie Journal: Blood Date: 2009-06-10 Impact factor: 22.113
Authors: M Wang; K Delasalle; L Feng; S Thomas; S Giralt; M Qazilbash; B Handy; J J Lee; R Alexanian Journal: Bone Marrow Transplant Date: 2009-07-27 Impact factor: 5.483