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Starting therapy for chronic lymphocytic leukemia (CLL) is often a very scary reality for patients. Patients with CLL may have been previously diagnosed but had not previously received treatment, or this is a brand new diagnosis that requires treatment. In this commentary, I share my thoughts on the importance of the oncology pharmacist for educating patients about receiving treatment with BTK inhibitors and proactive management of adverse events with these agents, particularly in patients with comorbidities.
Role of the Pharmacist
Pharmacists provide valuable education and insight on treatments and can have a direct impact on the different aspects of patients’ care while they are being treated for CLL. In my practice, I evaluate medication lists for patients to confirm that they are inclusive of all the medications they are taking, including supplements and nutritional products. We look for drug interactions that can pose therapeutic challenges with any of their treatment medications, especially if they will receive a BTK inhibitor. We may also be asked to look for baseline and follow-up laboratory test results as needed. Laboratory results can help inform the prescribing physician as to whether any dose or therapeutic adjustments are necessary. When prescription refills are picked up, I talk to patients about how they are tolerating the therapy and check for any adherence concerns. Since therapy with BTK inhibitors can be long term, I recommend to other pharmacists to continue to build a relationship and support patients with CLL so that they can be successful during their treatment journey.
I frequently have conversations with patients about financial concerns. Medications for CLL can be expensive, and patients are very anxious about receiving a treatment that may lead to financial debt. Pharmacists play a key role in helping to alleviate these concerns and assisting patients on gaining access to resources to cover some of the costs associated with their treatment.
Treatment of CLL With BTK Inhibitors
BTK inhibitors are oral medications currently available as monotherapy or in combination with anti‑CD20 antibodies for newly diagnosed as well as relapsed/refractory CLL. BTK inhibitors have significantly changed the treatment landscape for patients with CLL.
As a therapeutic class, BTK inhibitors are associated with the adverse events (AEs) of cytopenia, diarrhea, and fatigue. Ibrutinib was the first FDA-approved BTK inhibitor and so we have more experience with its AEs and patient tolerance profile, including a higher potential of cardiotoxicity, atrial fibrillation, bleeding risk, liver issues, and skin toxicities. Approximately 20% of patients can also become intolerant or resistant to ibrutinib. If AEs are not resolved with treatment breaks and dose reductions or in the event of treatment intolerance, a switch to a second-generation BTK inhibitor, such as acalabrutinib, may be a good option to discuss with the oncologist and the patient.
Second-generation BTKs like acalabrutinib and zanubrutinib have greater target specificity with lower off-target activity. These advancements really decrease the potential for cardiotoxicity, and overall, patients have experienced fewer AEs with them, resulting in better tolerance and fewer dose reductions required.
When talking to patients, I use drug education sheets for any given treatment. These are well laid out and easy for patients to read, and it gives me an opportunity to highlight the sections as I am addressing them with the patient. I also spend some time going over the specific AEs that they could experience while on their BTK inhibitor. On the patient education forms, I can also write information about how to manage specific AEs if they occur and how soon after an episode they should contact their healthcare provider.
Drug and Food Interactions for BTKs
All BTK inhibitors are metabolized through the liver and the cytochrome CYP3A mechanism. Therefore, there can be potential interactions with other drugs and even foods. I counsel patients receiving BTK inhibitors to avoid any grapefruit products and to avoid use of anticoagulants if possible. If patients require use of anticoagulant agent, I discuss with their oncologist either starting with a direct oral anticoagulant or, if they are receiving warfarin, switching to direct oral anticoagulant medications to decrease the potential for bleeding.
Acalabrutinib has significant interaction with proton pump inhibitors. I work with patients on their options for controlling their gastrointestinal reflux (eg, sleeping positions), which may provide them with some relief. If their gastrointestinal symptoms persist or worsen, we can use an H2 antagonist like famotidine, and if no other options are effective, I work with the oncologist to switch the patient’s medication from acalabrutinib to either ibrutinib or zanubrutinib, if that is an option.
Compliance: Challenges and Opportunities
It is important to ensure that patients are educated about taking their medication consistently and to remain adherent to their BTK inhibitor dose and schedule, especially since disruption in ibrutinib dosing may result in disease progression. To address compliance concerns, I may work with patients on setting up a dosing calendar, pill reminder alarms, phone apps, and dosing boxes. I may also watch for long lapses when patients refill their medications, which gives me an opportunity to reach out to them, check in, and provide them with additional support, if needed.
There are many challenges for patients with CLL, and as pharmacists, we have unique opportunities to help address these challenges with our patients. One of the biggest challenges patients experience is their insurance coverage for their prescription medication, in particular patients with Medicare where copays may be up to 30% (or $10,000-12,000 per year). Having those financial conversations can be terrifying for our patients. In my current practice, we have developed programs that help our patients look for different copay assistance programs offered by different grant foundations and drug manufacturers. We work closely with the oncologist and other members of the healthcare team to try and make treatment a reality for our patients.
Comorbidities can be a consideration with BTK inhibitors, especially since most patients with CLL will receiving treatment for potentially a long time. We look for changes in liver conditions that can compromise the way the BTK inhibitors are metabolized. In patients receiving ibrutinib who experience decline in their cardiac health (arrhythmias, atrial fibrillation) or a thrombotic event, I work with the oncologist to evaluate if acalabrutinib could be an option for those patients or if switching to a different class of therapy is necessary.
The role of pharmacists is constantly evolving in the management of patients with CLL. Strong communication with patients and their care teams is key to identifying treatment challenges and opportunities on how to address them. Asking open‑ended questions to patients may help to identify if they are experiencing AEs or had changes to their medications and to identify opportunities to improve outcomes. Once patients are stabilized on BTK inhibitors, they do not see their oncologist as frequently, but they still have routine contact with the pharmacist for their medication refills. That contact allows us to build those relationships needed for patients to feel very comfortable asking us questions, and we can help assess tolerance and their adherence to their medications, propose options and alternatives to manage AEs, or even escalate to their oncologist.
How do you help patients receiving treatment with BTK inhibitors achieve better outcomes? Please answer the polling question and join the conversation by posting a comment in the discussion section below.