TKI Selection in CML: Clinical, Economic Burden and Long-term Outcomes

While adherence to both first- and second-generation tyrosine kinase inhibitors (TKIs) is “suboptimal” in chronic myeloid leukemia (CML), second-generation TKIs incurred lower medical costs, according to a poster presented at the European Hematology Association 2021 Virtual Congress that assessed the clinical and economic burden of first-generation TKIs vs second-generation TKIs.¹

TKIs are the standard of care in chronic phase CML (CML-CP), and they are associated with high health care resource utilization and costs. The researchers assessed the clinical and economic burden of the first- and second-generation TKIs by using the Veteran’s Health Administration database. The study included 944 patients in the database between April 1, 2013, and March 31, 2018.

The majority of patients (78.9%) were on a first-generation TKI, while only 21.1% were on a second-generation TKI. Patients on the first-generation TKI had a higher comorbidity burden at baseline. Compared with patients on second-generation TKIs, patients on first-generation TKIs had higher rates of chronic obstructive pulmonary disease (19.7% vs 8.0%; P < .01), anemia (17.7% vs 11.1%; P = .02), gastrointestinal symptoms (28.5% vs. 18.6%; P < .01), cardiac dysrhythmias (15.6% vs. 7.5%; P < .01), coronary artery disease (26.3% vs. 13.6%; P < .01), and hypertension (55.7% vs. 43.2%; P < .01).

The researchers also found:

• Optimal adherence was slightly higher among the patients on first-generation TKIs (69.6%) compared with second-generation TKIs (62.2%; P = .04)
• Patients on second-generation TKIs had lower medical costs compared with patients on first-generation TKIs ($3162 vs $3906; P = .04)
• Patients on second-generation TKIs had higher all-cause pharmacy costs ($7214 vs $3895; P < .01)
• Patients on first-generation TKIs had higher CML-related costs ($2260 vs $1640, P < .01)
• Patients on first-generation TKIs had higher cardiac-related medical costs ($1365 vs. $665, P < .01)

The researchers attributed the higher pharmacy costs for patients on second-generation TKIs to the fact that the first-generation TKI imatinib became a generic drug during the study period.

In a second poster, researchers from Greece analyzed front-line TKI selection in CML. They investigated the role of early molecular response (EMR) in the long-term outcome based on the first-line TKI.²

“Treatment goal is the deepest molecular response,” the authors wrote. “However, the optimal time for this achievement that results in the best long-term outcome and the best chance for treatment-free remission remain under discussion.”

The retrospective, real-world study included 261 patients with CML-CP who received their diagnosis between 2005 and 2020. EMR data were available on 148 of the patients. Because 6 patients ended up changing TKI due to intolerance/toxicities, EMR was ultimately evaluated for 142 patients.

The first-line therapies evaluated were imatinib (n = 90), nilotinib (n = 43), and dasatinib (n = 9). A total of 113 patients achieved EMR: 76.6% on imatinib, 80.9% on nilotinib, and 100% on dasatinib. A total of 107 patients were on the same TKI 12 months after diagnosis and 103 patients remained on the same TKI for at least 18 consecutive months.

Prior to 12 months, all TKI changes were made due to grade ≥ 3 toxicities. Five patients on imatinib were changed due to rash, edema, and myalgias, and 1 patient on nilotinib due to gout and rash. At 18 months, 3 patients were switched due to toxicities (rash on imatinib, myocardial infarction on nilotinib, and pleural effusion on dasatinib), while 1 patient switched because they did not achieve optimal treatment response on nilotinib.

At 60 months of follow-up, the event-free survival was 85.3% for imatinib, 78.9% for nilotinib, and 28.1% for dasatinib.

“In terms of effectiveness, EMR can provide guidance at an early timepoint,” the authors concluded. “Although more potent TKIs are available, IM still appears to be satisfactory as frontline treatment choice taking into consideration the long-term safety profile.”

References

1. Russell-Smith TA, Verma S, Liu Y, Sikirica S, Janjan N. Retrospective real-world comparison of clinical and economic burden between first-generation and second-generation tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML). Presented at: EHA2021 Virtual Congress; June 9-17, 2021. Poster PB1520.

2. Tsonis I, Mellios Z, Dellatola M, et al. Chronic myeloid leukemia – the challenge of frontline TKI selection 20 years after imatinib. Presented at: EHA2021 Virtual Congress; June 9-17, 2021. Poster PB1516.