OBJECTIVES: To investigate the relationship between patient-reported outcomes and durability of response using data from a phase 2 study of single-agent ibrutinib for patients with previously-treated MCL. METHODS: The phase 2 SPARK study evaluated the efficacy and safety of single-agent ibrutinib in patients with MCL who had received a rituximab-containing regimen and had progressed after ≥2 cycles of bortezomib therapy. In this multicenter, single-arm study, patients were enrolled to receive 560 mg/day ibrutinib continuously until progressive disease (PD) or unacceptable toxicity. The primary end point was the overall response rate in response-evaluable patients, as assessed by an Independent Review Committee. Secondary end points included patient-reported outcomes (FACT-Lym). RESULTS: Overall, 25 of 110 evaluable patients (22.7%) were considered to have primary resistant disease (PD at first disease evaluation), with 85 of 110 (77.3%) considered as “responders”: 22 patients (20%) were considered to have moderate response (stable disease [SD] or better, but with PD within 12 months; MR group), and 63 patients (57.3%) were considered to have durable response (SD or better, maintained for >12 months; DR group). Median progression-free survival for the total evaluable population was 10.5 months; 4.1 months for the MR group and 16.8 months for the DR group. Additionally, 67 of 109 response-evaluable patients who had PRO results (61.5%) achieved a clinically-meaningful improvement in lymphoma symptoms based on a change of ≥5 points on the FACT-Lym, with 57 of the 80 “responders” who had a post-baseline FACT-Lym evaluation (71.3%) achieving this clinically-meaningful level of improved quality of life. CONCLUSIONS: Single-agent ibrutinib was highly efficacious in this study with a majority of patients responding to therapy and achieving long, durable remissions. Moreover, patients with clinical responses to ibrutinib also tended to show clinically-meaningful improvements in patient-reported outcomes.