Tyrosine kinase inhibitor interruptions, discontinuations and switching in patients with chronic‐phase chronic myeloid leukemia in routine clinical practice: SIMPLICITY

Abstract

SIMPLICITY (NCT01244750) is an observational study exploring tyrosine kinase inhibitor (TKI) use and management patterns in patients with chronic phase‐chronic myeloid leukemia in the US and Europe in routine clinical practice. Herein we describe interruptions, discontinuations and switching of TKI therapy during the initial 2 years of treatment among 1121 patients prospectively enrolled between October 1, 2010 and March 7, 2017. Patient characteristics were broadly similar between the imatinib (n = 370), dasatinib (n = 376), and nilotinib (n = 375) cohorts. Treatment interruptions occurred in 16.4% (year 1) and 4.0% (year 2) of patients, mainly attributed to hematologic intolerances. Treatment discontinuations occurred in 21.8% (year 1) and 10.2% (year 2) of patients, with the highest rate within the first 3 months for intolerance. Switching of TKI was seen in 17.8% (year 1) and 9.5% (year 2) of patients. Significant associations were found between TKI switching and female gender (year 1), age ≥65 years at diagnosis (year 2) and treatment with imatinib (year 2). Intolerance was the most common reason given for patients discontinuing and for switching TKI therapy; however resistance was also cited. Lack of response monitoring in routine clinical practice may have resulted in lower identification of resistance in this dataset. Data from SIMPLICITY suggest that, in routine clinical practice, intolerance and resistance to TKIs influence decisions to change treatment. Changes in TKI therapy are frequent, with nearly a third of patients discontinuing their first‐line TKI.

Treatment patterns and clinical outcomes of tyrosine kinase inhibitors in chronic‐phase CML in clinical practice: 3‐year European SIMPLICITY data

“…Patterns of treatment interruptions, discontinuations, and switching in this analysis were consistent with those seen for the overall SIMPLICITY cohort after 2 years of follow‐up, which showed that a higher proportion of patients experienced these events in the first year of treatment than in the second 7 . These trends showing a decrease in these events in the second year extended to the third year, with the lowest proportion of European patients experiencing interruptions, discontinuations, and TKI switching in the third year of treatment.…”

“…These trends showing a decrease in these events in the second year extended to the third year, with the lowest proportion of European patients experiencing interruptions, discontinuations, and TKI switching in the third year of treatment. As previously observed for the overall SIMPLICITY population, 7 the key drivers for treatment changes in the European cohort were intolerances to TKIs and, to a lesser extent, resistance to TKIs. Although the proportions of patients with changes in treatment for intolerance declined year‐on‐year, the contribution of resistance to discontinuation of treatment increased after the first year of treatment.…”

“…SIMPLICITY is a non‐randomized study: As such, there is a risk of selection bias and confounding factors, and results should be interpreted in the context of clinical practice, and comparisons with randomized trials made with caution 11 . Limitations specific to SIMPLICITY have been discussed previously 6,7 …”

“…The primary objective of SIMPLICITY is to understand TKI use and management patterns in routine clinical practice and treatment‐related outcomes. Previous analyses of SIMPLICITY have highlighted that National Comprehensive Cancer Network (NCCN) and European LeukemiaNet (ELN) recommendations on response monitoring have not been consistently translated into routine clinical practice, and that intolerance is the most common reason for treatment interruptions, discontinuations, and switching 6,7 . In the overall SIMPLICITY population, 18% of patients with at least 12 months of follow‐up had no documented cytogenetic response (CyR) or molecular response (MR) monitoring during the first 6 months of TKI treatment, with a higher proportion of patients in the European cohort receiving a CyR or MR test in the first 6 months than in the US cohort (87% vs 79%) 6 …”

Chronic Myeloid Leukemia in 2020

“…Median age at diagnosis of CML is approximately 56 to 57 years in Western countries as estimated from the EUTOS and SIMPLICITY registries. 38 , 39 Patients older than 70 years make up more than 20%. In developing countries with younger populations median age is less than 50 years.…”