What can we learn from the ENDURANCE trial? ENDURANCE is an important Phase III randomized trial and a valuable contribution to the myeloma literature. Every well-conducted study advances our field, regardless of whether the results are positive or negative. After carefully reviewing both the manuscript and the Supplementary Appendix, I believe the most important lesson extends beyond the question of 2 years versus continuous lenalidomide. Clinical trials should be interpreted according to the trial that was actually completed, not simply the trial that was originally designed. Although more than 1,000 patients entered Step 1, only 516 patients (47%) underwent the second randomization. The investigators acknowledged that maintenance enrollment fell short of the planned sample size (516 vs. 704 patients) and that the maintenance comparison would be underpowered because of lower accrual and fewer-than-planned events. These are not criticisms from outside observers, but limitations recognized by the investigators themselves. Randomization remains the cornerstone of Level I evidence, but it is not the only determinant of confidence. Adequate accrual, sufficient statistical power, protocol integrity, treatment separation, and appropriate interpretation are equally important when considering whether a study should redefine the standard of care. Before changing the treatment of tens of thousands of patients, we should ask whether the completed trial retained the statistical strength that the investigators originally considered necessary to answer the question. ENDURANCE provides important evidence supporting a fixed-duration maintenance strategy in the specific population studied. Whether its findings should be generalized to all patients, extrapolated to modern quadruplet-treated cohorts, or applied regardless of MRD status, genomic risk, or transplant strategy remains an important scientific discussion. Our mission is not to defend or criticize a trial. Our mission is to learn from every trial, understand both its strengths and its limitations, and use those lessons to design better studies and make better decisions for the patient sitting in front of us. 📌 The accompanying figure summarizes the trial design, patient attrition, protocol amendments, statistical considerations, treatment exposure, major strengths, key limitations, and the questions that remain unanswered. In Biology We Trust. 🧬 #MultipleMyeloma #Medtwitter