CML-475 Real-World Treatment Patterns Among Patients With Chronic Myeloid Leukemia in Chronic Phase (CML-CP) Cycling Through Multiple Tyrosine Kinase Inhibitors (TKIs) in the United States (US)

Background

While TKIs are mainstay therapy for patients with CML-CP, many are refractory/intolerant to treatment.

Objective

To describe real-world treatment patterns of CML-CP patients receiving third or later lines of therapy (3L+).

Methods

Retrospective chart review of data collected through online case report forms completed between 03/05/2021-06/14/2021 by physicians from a panel of US oncologists/hematologists treating ≥1 adult with CML-CP who reached 3L+ between 01/01/2013-11/30/2018.

Results

In total, 64 physicians (academic: 36%; community: 64%) compiled data for 164 patients in 3L+ (median age: 58; females: 45%; White: 65%; Sokal score: intermediate: 47%, and high: 13%). In 1L (median duration: 13 months), most patients received the first-generation TKI (1G-TKI) imatinib (82%), and 12% received a second-generation TKI (2G-TKI) among which dasatinib was most common (9%). In 2L (median duration: 12 months), 92% received 2G-TKI including dasatinib (47%), nilotinib (31%) and bosutinib (13%). In 3L (median duration: 33 months), 2% received 1G-TKI, 49% 2G-TKI, 41% the third-generation TKI (3G-TKI, ponatinib), and 7% other CML-CP treatments. At data collection, most patients were undergoing 3L (67%), 15 patients were observed with a 4L and 3 with 5L. Main reasons for treatment discontinuation in earlier lines, based on physicians' interpretation, were lack of efficacy (1L: 34%; 2L: 26%), resistance (both 27%), and intolerance (1L: 21%; 2L: 26%). Proportion of patients with last molecular response (MR; achieved and sustained) of MR² or better was 44% in 1L and 53% in 2L, and MR³ or better was 32% in both lines. Patients mainly cycled from 1G-TKI in 1L to 2G-TKI in 2L (81%), with 46% receiving imatinib and dasatinib in 1L/2L. From 2L to 3L, 46% cycled between 2G-TKIs and 39% switched from 2G-TKI to 3G-TKI.

Conclusions

Patients with CML-CP in 3L+ have rapidly cycled between 1G-TKI and 2G-TKI in 1L and 2L. Rates of MR³ did not improve between earlier lines, with lack of efficacy/resistance being the most important reasons for discontinuation; intolerance became more prevalent in 2L. Findings highlight the need for novel therapeutics with improved safety/efficacy to prolong treatment in earlier lines and for patients in later lines who exhaust treatment options quickly.