In terms of therapeutic value, imatinib remains the gold standard in CML

When selecting a cost-effective first-line tyrosine kinase inhibitor (TKI) for the treatment of chronic myeloid leukemia (CML), consider the treatment goal.

In terms of survival, generic imatinib remains the gold standard, Dr. Elias Jabbour said during a session at the Society of Hematologic Oncology annual meeting in Houston.

For treatment-free remission, generic dasatinib or another generic second-generation TKI is needed, but is not yet available in the United States, so generic imatinib is the current best choice, said Jabbour, professor of medicine in the department of leukemia at MD Anderson Cancer Center in Houston.

Before the availability of generic imatinib, that wasn’t the case, he noted, explaining that second-generation TKIs met the criteria for cost-effectiveness, but now — at about $35 a month or about $400 a year — imatinib is much cheaper than the roughly $250,000 a year that brand-name second- and third-generation TKIs can currently cost.

To have therapeutic value, any new TKI would need to cost between $40,000 and $50,000 per quality-adjusted life year, which is defined as the quality and length of life after a new TKI compared with the existing standard of care, Jabbour said.

And to qualify as a first-line treatment for CML, any new TKI must demonstrate superior efficacy to second-generation TKIs, in addition to meeting cost-effectiveness criteria.

“It is difficult to demonstrate a survival benefit today, but we need to improve the rate of deep and durable molecular remission,” he said.

An equivalent or better long-term safety profile over at least 7 to 8 years is also required.

Based on the current literature, none of the currently evaluated ITKs have met this standard, although some trials are ongoing.

In a recent editorial, Jabbour and colleagues presented treatment recommendations based on currently available data. They suggested using lower doses of tyrosine kinase inhibitors than those approved in first-line and subsequent treatments to reduce toxicity, improve treatment adherence, and reduce costs.

They also suggested that the lack of early molecular response might not justify a change in TKI, particularly when a second-generation TKI was used in first-line therapy.

When treatment-free remission is not a therapeutic goal or is unlikely, changing the TKI to improve the depth of molecular response, which has been shown to improve the likelihood of treatment-free remission, could do more harm than good, they argued.

Instead, consider reducing the dose to manage reversible side effects, they suggested, noting that generic imatinib, and possibly generic dasatinib and perhaps other second-generation generic TKIs, will likely offer 90% of CML patients an effective, safe, and affordable treatment that normalizes life expectancy and leads to treatment-free remission in 30% to 50% of patients over time.

Jabbour disclosed his ties to AbbVie, Almoosa Specialist Hospital, Amgen, Ascentage Pharma, Biologix FZ, Hikma Pharmaceuticals, Kite, Takeda and Terns.

Sharon Worcester, MA, is an award-winning medical journalist based in Birmingham, Alabama, who writes for Medscape Medical News, MDedge, and other affiliated sites. She currently covers oncology, but has also written on a variety of other medical specialties and health topics. She can be reached at [email protected] or on X @SW_MedReporter.