CML-085: Discontinuation of Tyrosine Kinase Inhibitor (TKI) Treatment in Patients with Chronic Myeloid Leukemia in Chronic Phase (CML-CP) in US Clinical Practice Following Updates to NCCN CML Practice Guidelines

Abstract

Context NCCN CML practice guidelines were updated in 11/2016 and 11/2019 to incorporate criteria for TKI discontinuation in patients with CML-CP. Objective To describe TKI discontinuation practices in the US following updates to NCCN CML practice guidelines and compare them to a previously conducted study (Ritchie et al. Leuk Lymphoma. 2019). Patients Using an online case report form by US oncologists/hematologists, patient charts were abstracted (11/2019-12/2019) from adult patients with CML-CP that discontinued TKIs (1/2017-12/2018) after achieving adequate responses. Physicians' assessment of adequate response (TKI duration, molecular response (MR), and MR duration) and relapse were described. Results 153 patient charts were obtained from 61 physicians (academic: 43%; community-based practices: 57%), mostly from large practices (57%), with over 10 years (y) of experience following subspecialty training (59%). They had treated a median of 30 patients with CML-CP in the last 2y. Most (56%) did not have access to precise tests used to detect BCR-ABL1 of ≥4.5 log when attempting TKI discontinuation. Patients that discontinued TKIs had the following characteristics: mean age 56 y, 60% male, 69% white, 96% with TKI discontinuation in first-line. Besides achieving adequate responses, the most common reasons for TKI discontinuation were patient request (54%) and adverse events (18%). Results from physicians' assessment of adequate response for TKI discontinuation were as follows: most patients had ≥3 y of TKI therapy (academic: 57%; community: 43%); most patients had MR4 (academic: 31%; community: 45%) or MR4.5 (academic: 48%; community: 30%); more patients had ≤1 y duration of MR (academic: 36%; community: 61%) than 2 y (academic: 25%; community: 17%), and ≥3 y (academic: 39%; community: 22%). 21% of patients (academic: 12%; community: 30%) relapsed after TKI discontinuation (treatment-free remission [TFR] failure; 66% relapsed within 1 y). Conclusion TKI discontinuation is mainly attempted in patients on first-line therapy (similar to Ritchie et al. 2019) and is being practiced without tools required to accurately monitor response. Despite updates to NCCN CML practice guidelines, there is heterogeneity in US practice regarding TKI discontinuation. In order to improve long-term TFR rates, broader application of practice guidelines is needed for optimal TKI discontinuation, particularly in community-based practices. Study sponsored by Novartis Pharmaceuticals Corporation. © 2020 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the 2020 ASCO Annual Meeting. All rights reserved.