Background: NCCN CML practice guidelines were updated in 11/2016 and in 9/2019 to include considerations for discontinuation of TKI therapy in patients (pts) with CML-CP. This study characterized TKI discontinuation practices in the US after these updates and drew parallels with a similar study conducted prior to these guideline updates (Ritchie et al. Leuk Lymphoma. 2019). Methods: Pt charts of adult CML-CP pts with TKI discontinuation (1/2017-12/2018) outside a clinical trial after achieving an adequate response were abstracted (11/2019-12/2019) via an online case report form by US oncologists/hematologists. Physicians’ assessment of adequate response (TKI duration, molecular response [MR], MR duration) and relapse were described. Results: 61 physicians (academic: 43%; community-based practices: 57%) contributed 153 pt charts. Most physicians were from large practices (57%), had > 10 years (y) experience since completing subspecialty training (59%), and treated a median of 30 CML pts in the last 2y; 56% did not have access to precise molecular response monitoring for BCR-ABL of ≥4.5 log when attempting TKI discontinuation. Pts with TKI discontinuation had mean age 56 years, were mostly male (60%), white (69%), and had TKI discontinued in first-line (96%). Most common reasons for TKI discontinuation were pt request (54%) and adverse events (18%), besides achieving an adequate response. Physicians’ assessment of adequate response for TKI discontinuation are reported in the Table. 21% of pts (academic: 12%; community: 30%) relapsed after TKI discontinuation (treatment-free remission [TFR] failure; 66% relapsed within 1y). Conclusions: Although NCCN CML practice guidelines provide guidance for discontinuation of TKI therapy, there remains heterogeneity in US practice and TKI discontinuation is predominantly attempted in first-line (similar to Ritchie et al. 2019). TKI discontinuation is being practiced without adequate sensitive tools mandated by practice guidelines to monitor response. Broader application of practice guidelines for optimal TKI therapy discontinuation in CML-CP pts is needed, particularly in community-based practices, to improve long-term TFR rates.