Clinical Outcome of Chronic Myeloid Leukemia Patients who Switch from First-line Therapy with a Second Generation Tyrosine Kinase Inhibitor to an Alternative TKI

2021 ◽  
pp. 106674
Author(s):  
Chen-En Ma ◽  
Sunita Ghosh ◽  
Catherine Leyshon ◽  
Nikki Blosser ◽  
Deonne Dersch-Mills ◽  
...  
10.36469/9899 ◽  
2015 ◽  
Vol 2 (2) ◽  
pp. 181-191
Author(s):  
Melea A. Ward ◽  
Gang Fang ◽  
Gang Fang ◽  
Kristy L. Richards ◽  
Christine M. Walko

Background: Research has shown that treatment interruptions are associated with worse failure-free survival in chronic myeloid leukemia (CML); however they are commonly used in clinical trials to manage adverse events. Objectives: This study assessed the comparative rates of treatment interruption and regimen change between patients initiating first-line therapy with a first-generation tyrosine kinase inhibitor (1GTKI) imatinib versus second-generation TKI (2GTKI), dasatinib or nilotinib, for the treatment of CML in clinical practice. Methods: This was a retrospective cohort study using the Humana Research Database. Patients with CML who were between the ages of 18 and 89 and newly initiated 1GTKI or 2GTKI therapy between June 1, 2010 and December 31, 2011 were included. Treatment interruption and regimen change were compared using multivariable Cox proportional hazard regression models. Treatment interruption was defined as a gap in any TKI pharmacy claim that was longer than an allowable refill gap plus days’ supply from the previous TKI medication claim. Regimen change was defined as 1) a prescription claim for a different TKI therapy, or 2) increase in dose for the same medication. Results: 368 patients met the inclusion criteria: 1GTKI n=237, 2GTKI n=131. Patients initiating therapy with a 2GTKI had a 48% higher risk of treatment interruption versus patients initiating therapy with a 1GTKI (hazard ratio=1.48, 95% confidence interval 1.08-2.02). The time to treatment interruption was significantly longer in patients initiating therapy with a 1GTKI. Approximately 19% of patients had a regimen change, but there were no differences in rates of regimen changes between the two generations. Conclusions: In this study from a large single health plan population, treatment interruptions were more common among patients initiating therapy with a 2GTKI, yet regimen change rates did not vary by generation of TKI. Future research should assess reasons for treatment interruption and investigate these associations in other populations.


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2569-2569
Author(s):  
Nancy Cribb ◽  
Tazmin Merali ◽  
Bonnie MK Donato

Abstract Abstract 2569 Background: New treatment options in chronic myeloid leukemia (CML) have become available in the past years. However, there is a scarcity of published data documenting how patients are treated as well as the impact of the treatment of CP-CML in Canada. Objective: To describe current treatment patterns and clinical outcomes of CP-CML patients receiving treatment in Canada. Methods: Treatment data on CP-CML patients was extracted from a cancer patient treatment summary database, ONCO-CAPPS. The database is comprised of treatment summaries of over 12,000 Canadian cancer patients from across the country. For the study, CP-CML patients aged 18 years or older, who received 400mg of imatinib as 1st-line treatment, and who completed at least 4 continuous weeks of this treatment between October 1, 2008 and December 31, 2009, were eligible for study inclusion. Results: A total of 301 patients met the selection criteria. At the time of review, 62% of patients had a confirmed diagnosis of CP-CML for 2 years or more. Of the CP-CML patients in the study who were prescribed 400mg of imatinib as their initial CP-CML treatment, 51% (155/301) received a 2nd line treatment option, either a dose modification or a change of therapy. Of those requiring 2nd line treatment, 32% (50/155) of patients received an increase in their imatinib dose, resulting in an average daily dose of 664 mg, and representing a 66% increase in the dose of imatinib. Average response times for patients who received an increase in imatinib dose for Complete Hematological Response (CHR) was 183 days, for Complete Cytogenetic Response (CCyR) was 671 days, and for Major Molecular Response (MMR) was 971 days. These response times exceed both Canadian Consensus Guidelines as well as the 2009 ELN (European Leukemia Network) recommendations. Furthermore, 45% (69/155) of patients receiving a 2nd line CML treatment experienced intolerance to imatinib 400 mg resulting in dose decrease or treatment interruption. Switching to second generation tyrosine kinase inhibitor agents (dasatinib or nilotinib) due to inadequate response, loss of response or intolerance to imatinib occurred in 20% of the population. Conclusions: Analysis of Canadian patients over time revealed that 51% of CP-CML patients initiated on 400mg imatinib received 2nd line treatment. The most frequent modification was due to intolerance. Of note, 32% received a dose escalation, which was more common than switching to a second generation tyrosine kinase inhibitor. Furthermore, response times observed amongst patients in this study whose imatinib dose was escalated exceeded timelines for treatment response determination as noted in both internationally and locally recognized treatment guidelines. Published research demonstrates that delays in achieving response are associated with increased risk of progression among patients with CML. Disclosures: Cribb: Drug Intelligence Inc.: Research Funding. Merali:Bristol-Myers Squibb Canada: Research Funding. Donato:Drug Intelligence Inc.: Research Funding.


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