7514 Background: While it has been established that attainment of a complete response (CR) after chemoimmunotherapy improves progression free survival (PFS), this has not been proven with the BTK inhibitor ibrutinib (IB). Most patients (pts) receiving IB achieve a partial response (PR) at best, and multiple trials have focused on deepening responses. Here we investigate the association of depth of response at one year and PFS in CLL pts on IB. Methods: This was a retrospective study of pts with CLL enrolled in 4 sequential clinical trials of IB as a single agent or in combination with ofatumumab at the Ohio State University. Response was evaluated by two independent investigators using International Workshop on CLL 2008 guidelines if bone marrow was available; if no marrow was available, clinical response was used. A landmark analysis was performed at response assessment at 12 +/- 2 months. PFS was calculated from this response assessment to progression or death. The method of Kaplan-Meier and Cox models were used to estimate PFS. Results: The cohort was comprised of 237 pts enrolled between July 19, 2010 and March 24, 2014 with median number of prior therapies 3 (range 0-13). Median age was 65; 82% IGVH unmutated, 36% with del(17p), and 54% with complex karyotype. At month 12 assessment, 5% of pts had CR, 3% CR with incomplete marrow recovery (CRi), 77% PR, 12% PR with lymphocytosis, and 3% stable disease. With a median follow-up of 48 months, the median PFS was 52 months (95% CI: 42-70) with no significant difference among response groups (p = 0.23). However, PR pts with lymph nodes (LN) ≥3cm had significantly higher risk of progression than pts with LN < 3cm (median PFS 42 vs. 68 months; hazard ratio = 1.6, p = 0.03 from multivariable model). Conclusions: There was no significant difference in PFS between CR and other response groups. However, a significant difference was found in PR pts with LN ≥3cm vs. LN < 3cm. This suggests that, unlike with chemoimmunotherapy, attainment of a CR with IB is not critical, however, those patients with significantly enlarged nodes after 1 year of therapy have shorter PFS. Combination therapy studies without the goal of therapy discontinuation may focus on elimination of bulky nodal disease rather than attainment of CR for all patients.