Patient Goals and Concomitant Needs Help Guide TKI Selection in CML

The variety of approved TKIs present patients and physicians with multiple similar options for the treatment of chronic myeloid leukemia (CML); however, outlining the long-term individual goals of patients can aid in selecting optimal treatments, according to Jorge Cortes, MD.

“I don't like reserving things for later. Sometimes we can be blinded by focusing on short-term goals. What's important is the long-term goals of patients and being aggressive and ambitious about the potentials that are now possible,” Cortes said in an interview with OncLive®.

During the conversation, Cortes also touched on the FDA approval of the generic, small-molecule formulation of dasatinib (Sprycel) in November 2025 and its clinical implications for CML management.¹

He discussed how the newly approved formulation of dasatinib will play a pivotal role, specifically in helping patients who require concomitant gastric acid–reducing agents to continue their TKI treatment. In addition to dasatinib, Cortes highlighted TKIs like imatinib (Gleevec), nilotinib (Tasigna), bosutinib (Bosulif), and asciminib (Scemblix) and their roles in the CML treatment paradigm.

Cortes is the director of the Augusta University Georgia Cancer Center.

OncLive: How do you approach TKI selection and sequencing in CML?

Cortes: When thinking about initial therapy, the most important thing [to remember is]: what are the patient's goals and needs? There are some guidelines and recommendations that suggest that you base [TKI selection and sequencing] on so-called risk classification. To me, what really matters is the patient's goals. Some patients are interested in having the best chance of stopping therapy. Eventually, some patients are more interested on just having the lowest possible [adverse] effects [AEs], the least toxicities, and the best quality-of-life [QOL]. [For] some patients, cost [may be] their main consideration. Ultimately, the goals of patients [help me] decide what may be the best option.

Sometimes [this approach] leaves me with 2 or 3 [treatment options, with] other factors playing a role. For example, schedule of administration [is a factor]. These are simple things, but when you have [many treatment] choices, if [one treatment] makes it easier and more convenient for the patient, especially [considering] adherence issues, this would be important. Comorbidities of patients is another important element. Comorbidities or past histories may predispose the patient to certain toxicities that you may see more with one drug than with another.

[Subsequent therapies] depend on what happened first [with initial treatment], whether [patients] responded, whether they had AEs, and what kind of AEs. [TKI treatment selection and sequencing] is getting a little bit more complex. Patient goals [remain important] but also must be [contextualized] regarding what's happened with the disease,

What differentiates different TKIs like dasatinib, ponatinib, and imatinib from one another? What improvements have been made with later-generation agents?

In terms of efficacy, let me start by saying that all of these drugs are good, [and thus] we have the luxury of [having multiple treatment options in CML]. We have good drugs and probably better drugs, but they're all good in terms of efficacy, and there are 3 layers [to consider].

[Most second-generation TKIs] are at the same level of efficacy, a little bit above imatinib. [Regarding] safety, imatinib has the lowest risk of cardiovascular toxicities, arterial occlusive events, heart attacks, strokes, and other related AEs. [Imatinib] is a good choice for patients that have many comorbidities like diabetes, hypercholesterolemia, and strokes. In terms of other AEs, asciminib has proven to be extremely well tolerated, so when [factors like] QOL, AEs, and minimal toxicity [are important considerations]. Asciminib tends to be a good choice due to its tolerability.

Among the second-generation TKIs, [treatment selection] depends on risk factors. Dasatinib can cause more pleural effusion, and bosutinib can cause more diarrhea. You have to put [these risks] into context and determine what fits better with the patient's lifestyle, history, and preferences.

What are the clinical implications of the recent FDA approval of the generic, small-molecule dasatinib formulation for patients who require concomitant gastric acid-reducing agents?

One of the problems with some TKIs, especially dasatinib, nilotinib, and bosutinib, is that they need an acidic stomach for good absorption. When you have a patient who has gastric ulcers or gastritis, needing antacids and proton pump inhibitors [PPIs], then [using these TKIs] becomes a problem since the patient needs to be taking those medications, but the absorption of the drug may be less. Dasatinib is a popular drug, we use it frequently, either as frontline or second-line [therapy], and but it has that limitation [with patients who need acid-reducing agents].

Unfortunately, these issues with reflux and gastritis are not that uncommon. The new formulation [of dasatinib that was approved]—and there's another one that is that is probably coming—tried to address this [absorption] issue for patients who may benefit from dasatinib, who maybe responding well already on dasatinib, but need these [gastric acid-reducing] medications. If you are using just antacids, you can time them so that you use them, then wait and give the dasatinib. However, when patients need PPIs, then it's not going to be a timing issue. [PPIs are] just going to compromise the absorption [of dasatinib].

[The approval of the new formulation is a] niche indication for this subset of patients only, but for this subset of patients, it becomes very important, because it allows better QOL. [Thus], rather than having to change medications when the medication is otherwise working, patients can consider this formulation that enables concomitant administration [with PPIs].

How will the approval impact which dasatinib formulation decision-making for patients with CML?

The new formulation [does not] change my use of dasatinib as a whole, but it makes it easier in those patients that are having [gastric acid] problems. [Now with the approval], it’s less likely that I'm going to have to change [TKIs for patients]. I do have some patients where changing [TKIs] is undesirable since it's working and it's otherwise well tolerated, but the patient needs a PPI. The [generic, small molecule formulation of dasatinib] gives you that option for this subset of patients. [The approval] probably won't make me use dasatinib more often, but it will allow my patients on dasatinib to have an improved QOL. It’s one thing if you’re battling CML and you're having a good response, but if still having to suffer with reflux and upset stomach all the time, [this formulation helps patients with that issue].

What are the next steps for TKI and CML research?

One of the areas where CML is still deficient is in treatment discontinuation. We've made tremendous progress since we started using TKIs. We were happy with the progress, but we just assumed that the patients will be taking them for the rest of their lives. When we realized that there was a subset of patients who could stop therapy, that became fantastic, but the reality is that today is only roughly 25% to 30% of all patients [with CML] can successfully stop therapy. That's good, but it's not even half of patients.

We definitely need to improve [treatment discontinuation rates]. The new generation of drugs like frontline asciminib is going to increase [treatment discontinuations] to some extent, but it's likely that we're going to need something else. There's different [immune-modulating approaches] that are being explored to try to get to that point. There's an interesting phase 2 study [NCT03610971] combining TKIs with ruxolitinib [Jakafi], which seems to be showing promising results.² This is an area of research that is interesting, active and much needed.

[Another important area of research] is looking patients who have ASXL1 mutations at the time of diagnosis. It's a small subset of patients—about 10%—but they don't respond as well. These patients tend to lose their response more than patients that don't have ASXL1 mutations, we need to figure out what's the best way to treat these patients. There is some preliminary suggestion that combining a conventional TKI and asciminib may improve responses [for these patients], but that needs to be confirmed and expanded.

References

1. Treatment free remission after combination therapy with ruxolitinib plus tyrosine kinase inhibitors. ClinicalTrials.gov. Updated January 29, 2026. Accessed March 19, 2026. https://clinicaltrials.gov/study/NCT03610971