In multiple myeloma (MM), it remains unclear whether the depth of response correlates with progression-free survival (PFS) and overall survival (OS). We updated long-term follow-up data on the two previously published multi-centre phase-II trials in patients with relapsed or refractory MM using thalidomide +/- IFN alpha-2B (n = 75, median follow-up 6.1 years) celecoxib-thalidomide combination (n = 66, median follow-up 4.0 years), and assessed the predictors of durable response and impact of depth of response. Twenty-seven of the 141 (19%) patients remained progression-free beyond 24 months. The most significant baseline predictor for durable PFS and OS was a serum beta(2)-microglobulin <or=3.0 mg/L. The median PFS for patients who achieved complete remission/very good partial remission, partial remission and stable disease were 69.4, 13.6 and 4.1 months, respectively (p < 0.001). The OS for these groups were >69.8, 35.4 and 11.7 months, respectively (p < 0.001). These findings support the therapeutic goal of achieving 'maximum depth of response' in patients with relapsed myeloma.