Outlining Historical Standards for Treatment in Newly Diagnosed CML
The toxicity profile of interferon and the limited availability of transplantation established a need for TKI development for chronic myeloid leukemia.
According to Jorge Cortes, MD, director, and Cecil F. Whitaker Jr., GRA Eminent Scholar Chair in Cancer of the Georgia Cancer Center, outcomes with historical standards for patients with newly diagnosed chronic myeloid leukemia (CML), which included interferon and transplantation, were not great overall.
In an interview with CancerNetwork®, Cortes discussed limitations associated with standards of care prior to the FDA approval of imantinib (Gleevac), which prompted the development of the agent, as well as subsequent generations of tyrosine kinase inhibitors (TKIs) for the treatment of this patient population.
Toxicities associated with interferon made the agent untenable, particularly among the 20% to 25% of patients who experience complete cytogenetic responses, with low response rates. Additionally, although transplantation is comparatively better and considered curative, limits due to age, donor availability, toxicities, and complication rates made it an unattractive option then, although the modality has since improved. The development and subsequent approval of imantimab in 2000 sought to overcome these limitations and bring enhanced outcomes to a group of patients who were left with few options.
Transcript:
In the standard of care prior to TKI development, there were 2 options: 1 was interferon, usually combined with low doses of cytarabine, and the other was transplant. Neither one was great. Interferon was [quite] toxic, and it had low response rates. The significant responses, which are what we call the complete cytogenetic responses, happened in 20% to 25% of patients with a lot of toxicity.
The other option was transplant, which is [better]. Transplant is curative, but particularly in those days, it was still limited [due to] age, availability of donors, and the toxicity and even the mortality rate, which has improved since then. In those days, we were facing difficult choices for patients, and many did not have great options. The outcomes were not good, overall.
Reference
Center for Drug Evaluation and Research: Application Number: NDA 21-335. FDA. May 10, 2001. Accessed September 3, 2025. https://tinyurl.com/44xh2u9j
