For Treatment Value, Imatinib Remains the CML Gold Standard

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

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

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

Prior to the availability of generic imatinib, that wasn’t the case, he noted, explaining that second-generation TKIs met the cost-efficacy criteria, but now — at about $35 per month or about $400 per year — imatinib is far less expensive than the approximately $250,000 per year that brand-name second- and third-generation TKIs can currently cost.

To have treatment value, any new TKI should cost $40000-$50000 per quality adjusted life year, which is defined as the quality and duration of life after a novel TKI vs with the existing standard of care, Jabbour said.

And to qualify as a frontline therapy for CML, any new TKI should show efficacy superior to second-generation TKIs, in addition to meeting the cost-effectiveness criteria.

“It is hard to show survival benefit anymore, but we need to improve on the rate of durable deep molecular remission,” he said.

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

Based on the current literature, none of the TKIs currently being evaluated has met that standard, although some trials are ongoing.

In a recent editorial, Jabbour and his colleagues outlined treatment recommendations based on the currently available data. They suggested using lower-than-approved doses of TKIs in both front-line and later therapies to reduce toxicity, improve treatment compliance, and reduce costs.

They also suggested that the absence of an early molecular response might not warrant changing the TKI, especially when asecond-generation TKI was used first-line. 

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 eventually generic dasatinib and possibly other genericsecond-generation TKIs, will likely offer 90% of patients with CML an effective, safe, and affordable treatment that normalizes life expectancy and leads to treatment-free remission in 30%-50% of patient over time.

Jabbour disclosed ties with 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, writing for Medscape Medical News, MDedge, and other affiliate sites. She currently covers oncology, but she has also written on a variety of other medical specialties and healthcare topics. She can be reached at sworcester@mdedge.com or on X @SW_MedReporter.