@article{Marc Buyse_Stefan Michiels_Pierre Squifflet_Kathryn J. Lucchesi_Kristoffer Hellstrand_Mats L. Brune_Sylvie Castaigne_Jacob M. Rowe_2011, place={Pavia, Italy}, title={Leukemia-free survival as a surrogate end point for overall survival in the evaluation of maintenance therapy for patients with acute myeloid leukemia in complete remission}, volume={96}, url={https://haematologica.org/article/view/6036}, DOI={10.3324/haematol.2010.039131}, abstractNote={<strong>Background</strong> In trials designed to evaluate new therapies for hematologic malignancies, end points such as leukemia-free survival are often used as surrogates for overall survival in acute leukemia. We aimed to assess whether leukemia-free survival is an acceptable statistical surrogate for overall survival when applied to remission maintenance therapy for acute myeloid leukemia.<strong>Design and Methods</strong> Data were analyzed from a randomized Phase III trial of remission maintenance immunotherapy with histamine dihydrochloride plus low-dose interleukin-2 <em>versus</em> no treatment in adults with acute myeloid leukemia. A two-stage surrogate validation model was applied in which correlations between Kaplan-Meier estimates of leukemia-free survival and overall survival, and between log hazard ratios reflecting treatment effects were analyzed. Country of patient enrollment was the unit of analysis.<strong>Results</strong> Kaplan-Meier estimates of overall survival at 36, 48, and 60 months and leukemia-free survival at 24 months were reasonably correlated (R<sup>2</sup> ranging from 0.44 to 0.84) both for the overall (n=320) and first complete remission (n=261) populations. The effects of histamine dihydrochloride/interleukin-2 on log hazard ratios for leukemia-free survival and overall survival were well correlated (R<sup>2</sup>=0.88–0.93).<strong>Conclusions</strong> The significant correlations between overall survival and the surrogate end point (leukemia-free survival) and between the effect of histamine dihydrochloride/interleukin-2 on leukemia-free survival and overall survival satisfy the two-stage surrogate validation model. <em>(<a href="http://ClinicalTrials.gov">ClinicalTrials.gov</a> Identifier: <a class="external-ref external-ref-type-clintrialgov" href="/lookup/external-ref?link_type=CLINTRIALGOV&amp;access_num=NCT00003991&amp;atom=%2Fhaematol%2F96%2F8%2F1106.atom">NCT00003991</a>)</em&gt;}, number={8}, journal={Haematologica}, author={Marc Buyse and Stefan Michiels and Pierre Squifflet and Kathryn J. Lucchesi and Kristoffer Hellstrand and Mats L. Brune and Sylvie Castaigne and Jacob M. Rowe}, year={2011}, month={Aug.}, pages={1106-1112} }