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Fadi Haddad, MD, discusses TKI adherence barriers, adverse effect management, and the role of alternative TKI formulations in CML.
Consistent, daily adherence to oral TKIs is essential for achieving deep responses, treatment-free remissions (TFR), and long-term survival in chronic myeloid leukemia (CML). Proactively identifying and managing adverse effects (AEs) is one of the most practical ways to keep patients on therapy, according to Fadi Haddad, MD.
There are currently 6 TKIs that are approved for the treatment of CML, with the most recent
"There's no right or wrong answer, but [patients] need to pick the time of the day [that] they think they will be able to commit to the drug most and just stick to that. Put alarms, put reminders, put the pill box next to your bed. If it's better to take it at 5 AM, take it at 5 AM; [if] it's better to take it at 10 PM, take it at 10 PM," Haddad said in an exclusive interview with OncLive®. "Ultimately, improving [TFR], responses, [and] survival will depend on how much the patient is exposed to the drug and is compliant [with] the drug."
In the interview, Haddad discussed common barriers to TKI adherence, dose reduction and therapy changes as strategies for managing AEs, and where
Haddad is an assistant professor in the Department of Leukemia and co-leader of the Section of Chronic Myeloid Leukemia at The University of Texas MD Anderson Cancer Center in Houston.
Haddad: Adherence is extremely important with oral TKIs because studies have shown that people who are not adherent have [lower response rates] than people who are adherent, because in cancer in general, skipping treatment may ultimately lead to disease resistance [and] disease progression. Patients should, as much as possible, remain adherent every day [and] not miss the drug. Some of the challenges we face could be particularly in patients who are younger and busy, who travel and go on vacation a lot, [or] have families [and] work commitments.
One other cause [TKI adherence] that sometimes might be overlooked is AEs. As physicians, our duty is to ask our patients about AEs at each visit, but for our patients: If the physician does not ask you, please be proactive. Tell your physician about any AE that you are experiencing, because you might think that this is not related to the drug, [when] in fact it could be related to the drug.
We do see a lot of patients [with] fatigue, bone pain, muscle pain, [and] aches that could be attributed to various reasons, but maybe at the end it could be as simple as [those AEs being] drug-related. In that case, [for] patients who are in a good remission, we can reduce the dose a little bit. This could help with these AEs and could potentially help compliance, because patients who are having AEs ultimately will be discontinuing [or] interrupting medications, [which] will eventually lead to [worse] outcomes.
AEs [are] an important thing to keep an eye on. In patients who develop AEs, we need to either reduce the dose or sometimes change therapy to make sure patients are more comfortable with the drug [and] have low AEs; therefore, they can remain compliant for a longer period of time. This will eventually translate into better long-term outcomes.
We have 6 drugs that are FDA-approved. All 6 are approved in the second- or third-line-plus [setting], but imatinib [Gleevec], dasatinib [Sprycel], nilotinib [Tasigna], bosutinib [Bosulif], and asciminib are approved in the frontline setting.2 At the end of the day, all TKIs provide patients with similar long-term survival. Since we have a lot of drugs, we have a lot of treatment options, [so] at the end, our patients are doing great. This is a privilege we have in CML that we may not have in other cancers.
Obviously, newer drugs lead to faster, deeper remissions [and a] higher potential for [TFR] and treatment discontinuation. However, it's also important to tailor our treatment to the AE profile of that drug and the comorbidity profile of our patients. It's important to look at our patients' age [and] comorbidities, and then match this profile to a certain drug profile to make sure we limit the risk of AEs, and our patients achieve their desired goal of therapy.
There are a couple of other formulations. Most of these [TKIs] are oral tablets, but there are other oral forms, like liquid formulations, and there are some disintegrating formulations [that] you put under the tongue [and] they dissolve. These [alternative TKI formulations] are helpful in settings, particularly [for] patients who are not able to swallow. We rarely encounter those in clinical practice; patients with chronic phase disease are mostly doing fine.
[Alternative oral TKI formulations] could be a better formulation for patients who are severely sick, maybe with advanced-phase CML or Philadelphia chromosome [Ph]–positive [acute lymphoblastic leukemia (ALL)], where patients could be sick [and] having complications like infections [or] mucositis. [It could also help] children, because some children have Ph-positive ALL, and some adolescents or young kids can have chronic-phase CML as well. In these patient populations, disintegrating formulations or liquid formulations can be helpful.
There have been a few of these formulations in development, [and] many of them are already available for our patient population. I don't think there's anything that is exciting coming in the future for these formulations. What we have in [CML] is more than enough. We have many [options], between disintegrating [and] different types of oral formulations, but also liquid formulations that are already available. I don't think that newer formulations are needed, because what we have already covers the needs of our patients. The need for the future is to develop better CML drugs that have better efficacy, better safety, and higher remission rates.
Editor's Note: This transcript has been edited for grammar and clarity using artificial intelligence tools.
