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FAQ: Multidisciplinary Care for CLL
FAQs: Multidisciplinary Care During BTK Inhibitor or Venetoclax-Based Therapy for Patients With CLL

Released: March 20, 2023

Expiration: March 18, 2024

Victoria Nachar
Victoria Nachar, PharmD, BCOP
Caitlin R. Rausch
Caitlin R. Rausch, PharmD, BCOP
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Key Takeaways
  • Regular follow-up and monitoring of patients during treatment with venetoclax-based therapy or BTK inhibitor therapy is critical for adverse event management and treatment adherence.
  • Prior authorization is generally required for venetoclax-based therapy or BTK inhibitor therapy, and healthcare professionals may be required to navigate insurance requirements, aid in securing financial assistance, and provide additional documentation as needed.
  • There may be required holds for venetoclax or BTK inhibitors throughout the treatment course because of inpatient care, medications, surgery, or adverse effects but the patient’s care team should work to ensure that treatment is continued as closely as possible to the intended regimen.

In this third of 3 commentaries, expert pharmacists Caitlin Rausch, PharmD, BCOP, and Victoria Nachar, PharmD, BCOP, answer questions from a live webinar on best practices in the management of patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). The first commentary features a brief overview of key considerations for optimal use of BTK inhibitors and venetoclax plus CD20-targeted antibody therapy in patients with CLL/SLL. The second commentary in this series includes answers to additional questions asked during the live event.

When considering treatment options for patients with newly diagnosed CLL, what regimens do you prefer? Do you prefer to use obinutuzumab or rituximab for combination therapy?

Victoria Nachar, PharmD, BCOP:
In our clinic, we typically use a single-agent BTK inhibitor in the frontline setting. These agents produce durable, long-lasting responses. It is not clear whether adding rituximab or obinutuzumab increases the depth of response to BTK inhibitors, so we do not recommend a BTK inhibitor plus a CD20-targeted antibody at this time. My preferred BTK inhibitor is either acalabrutinib or zanubrutinib, given the superior toxicity profile of both second-generation agents. My decision between these 2 agents is usually based on whichever costs less for patients, as they will be on this therapy until progression.

When considering venetoclax-based therapy for a patient with newly diagnosed CLL, we pair venetoclax with obinutuzumab. This combination seems to provide deeper responses than venetoclax with rituximab and may lead to a longer remission.

How often do your teams reach out to patients with CLL to assess their adherence to these novel therapies?

Caitlin Rausch, PharmD, BCOP:
At my institution, we have a pharmacist-run oral chemotherapy clinic to support patients who are starting treatment for CLL. Patients receiving venetoclax have office visits every week so there is less need for additional follow-up until after they complete ramp-up dosing and remain on venetoclax 400 mg/day. Once they stabilize, the pharmacists reach out monthly and then every 3 months until the full course of venetoclax therapy is complete.

For patients who are beginning therapy with a BTK inhibitor, we follow up with patients weekly during their first month of BTK inhibitor therapy. After that, we follow up every 3 months during the first year to serve as a consistent point of contact since most patients will be seen less frequently by their physician at this point in their care.

Regular follow-up and monitoring of patients during the early stages of BTK inhibitor therapy is critical, as these drugs can cause adverse events such as nausea, diarrhea, headache, and fatigue. By reaching out to patients weekly during their first month of therapy, any adverse events can be identified early and managed appropriately, which can improve patient outcomes and adherence. Beyond this initial month of therapy, having regular touch points allows us to stay up to date on any new medications the patient may need to begin or other adverse events they may be experiencing, such as hypertension or bleeding and bruising.

Victoria Nachar, PharmD, BCOP: 
In my experience, patients who receive BTK inhibitor therapy long term need ongoing monitoring and support. Most practices, including mine, could do better at reaching out to these patients long term. Although adherence is often closely monitored during the early stages of treatment, it is important to recognize that patients may face a range of challenges and barriers to adherence over time; in particular, those patients who respond well to BTK inhibitors and may remain on therapy for many years are likely to become less adherent over time. We need to keep assessing patients over the long term. 

A multidisciplinary approach that involves physicians, physician associates/physician assistants, nurses, pharmacists, and other members of the healthcare team can be helpful in addressing these challenges and ensuring that patients receive the support they need to stay on track with their treatment. 

Is prior authorization required for BTK inhibitors or venetoclax/obinutuzumab?

Caitlin Rausch, PharmD, BCOP:
Prior authorization requirements can vary, but when patients are diagnosed with CLL, prior authorizations usually are required for any of the BTK inhibitors (ibrutinib, acalabrutinib, or zanubrutinib) and for venetoclax combinations. Prior authorization for ibrutinib and venetoclax are usually approved. Now that acalabrutinib and zanubrutinib are preferred agents in treatment guidelines, prior authorization approval is easier, but some insurers prefer ibrutinib first. 

The prior authorization process may be easier than some for these medications, but healthcare professionals may still need to navigate insurance requirements, advocate for their patients, and provide additional documentation as needed. Once approved by insurers, copays for these medications can still be a challenge for many patients, given the average age of our CLL patients. Obtaining patient assistance through foundations or the manufacturer is often needed as well.

If a patient with CLL is admitted inpatient, some of their medications may not be available on the formulary. How harmful is missing a dose?

Victoria Nachar, PharmD, BCOP:
The impact of missing a dose of medication for a patient with CLL can vary depending on several factors, including the patient's disease status and the length of time the patient has been on the medication. In general, if a patient misses 1 or 2 doses of a BTK inhibitor, it is unlikely to be harmful in the long term. However, for patients with a history of poor adherence or ongoing adherence issues, missing doses can affect long-term treatment outcomes, including progression-free survival and overall survival. Sometimes, a patient is admitted for a particular reason, like infection, that would require treatment to be held anyway, and in that case, a few missed doses is likely not a problem.

Caitlin Rausch, PharmD, BCOP:
I agree. If a patient with CLL is inpatient and their prescribed medication is not available from the formulary, their healthcare team should work to ensure that patient’s treatment is continued as soon as possible, if appropriate. There may be required holds for medications, surgery, adverse events, or other reasons. On the clinical trials of these regimens, patients were required to hold therapy for some of these reasons as well. Holding therapy once in a while is fine—and may even be preferable to mitigate any potential adverse events—but certainly missing multiple days of medication regularly is not what we want and would likely affect patients’ outcomes.

Your Thoughts?
What challenges have you encountered in using BTK inhibitors or venetoclax plus a CD20-targeted antibody in your patients with CLL? Share your comments below!

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Poll

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Which of the following aspects of using BTK inhibitors or venetoclax-based therapy for your patients with CLL/SLL has been most challenging for you?

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