The most essential requirement for a valid MRI outcome measure is that its findings are predictive of future clinical outcome, especially sustained progression in disability.
Reduced-intensity-conditioning allotransplantation produces sustained progression-free survival and overall survival (40%-60 40%-60years), equivalent to the cure of the disease, even in cases with adverse biomarkers.
The author found, between 15.8 and 42.2 % of patients experienced sustained progression based on the definitions using EDSS as the outcome, but nearly 50%% of these patients failed to maintain sustained progression for the duration of follow-up.
92 Results from the clinical effectiveness AFFIRM trial 93 are very favorable, with Natilizumab reducing the risk of sustained progression of disability by 42%, with the cumulative probability of progression being 17% compared to 29% in the placebo group.
The risk of 24-week sustained progression of disability was also reduced significantly among patients receiving DMF BID (29%) and TID (32%) compared with patients in the placebo group.
The risk of 12-week sustained progression of disability over 2 years was reduced significantly among patients receiving DMF BID (32%) and TID (30%) compared with patients in the placebo group.
In the AFFIRM study, 23 Tysabri® (NA); administered to 627 patients with RRMS at a dose of 300 mg every four weeks for more than two years, produced a reduction of sustained progression of disability by 42%.
More recent findings [ 21] suggest that even a consistent effect of on-study relapses on subsequent "sustained progression" could not be interpreted as evidence for a link between relapse frequency and the accumulation of true, unremitting disability.
In a subgroup analysis that excluded patients on natalizumab, the cumulative probability of progression was 10% for the 10 patients in the PLP10 group and 70% for the 12 patients in the placebo group, representing a relative 86% decrease in the risk of the sustained progression of disability in the PLP10 group (unadjusted log-rank p=0.006; adjusted HR, 0.11; 95% CI 0.01 to 0.97, p=0.047).
At 2 years, the cumulative probability of disability progression was 10% in the PLP10 group and 70% in the placebo group, which represents a decrease of 60% points or a relative 86% decrease in the risk of the sustained progression of disability within the PLP10 group (adjusted HR, 0.11; 95% CI 0.01 to 0.97, p=0.047).
Recent advances that incorporate combination chemotherapy and the anti-CD20-targeted agent rituximab (Rituxan) have improved the clinical outcome of patients diagnosed with diffuse large B-cell lymphoma (DLBCL), but only 60% of all DLBCL patients are potentially cured and achieve sustained progression-free survival (PFS).
