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FAQs: BTKi in MCL
FAQs: BTK Inhibitors in MCL

Released: January 24, 2024

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Key Takeaways
  • It is important to tell patients that acalabrutinib and zanubrutinib have similar efficacy but slightly different safety profiles that may influence individualization of treatment recommendations.
  • Pirtobrutinib is approved for patients with relapsed/refractory MCL after 2 or more lines of systemic therapy, including a BTK inhibitor.
  • Limited data suggest that pirtobrutinib is active as initial systemic therapy for MCL, but more data are needed.

In this commentary, Ann S. LaCasce, MD, MMSc; John P. Leonard, MD; and Matthew Lunning, DO, FACP, address clinical questions posed by the audience during a webinar titled “An MCL Quiz Game: Experts Review New and Emerging Therapies to Optimize Clinical Outcomes” held during the ASH 2023 annual meeting.

How do you choose between acalabrutinib and zanubrutinib in your clinical practice?

Ann S. LaCasce, MD, MMSc:
If I have a patient who is willing to receive an orally bioavailable drug indefinitely, I will preferably recommend zanubrutinib. Although acalabrutinib-associated headaches usually resolve within 1-2 months when managed appropriately, some patients do not have the patience for this symptom to resolve. It is important to inform patients that acalabrutinib and zanubrutinib have similar efficacy. However, I have seen more cytopenias and hypertension with zanubrutinib compared with acalabrutinib. So, if a patient has cytopenias and/or uncontrolled hypertension, I will be inclined to favor acalabrutinib. In all, it is important to tailor treatment to the individual patient, but most times, the choice between acalabrutinib and zanubrutinib has a lot to do with insurance reimbursement.

John P. Leonard, MD:
I agree. I think, often, insurance reimbursement is the biggest factor in the choice between acalabrutinib and zanubrutinib.

Matthew Lunning, DO, FACP:
I think it is more about an issue with insurance coverage rather than reimbursement, because both are orally available agents.

What are your thoughts on the potential use of pirtobrutinib in earlier lines of therapy, and what are some of the challenging sequencing issues that may come up with its use after a covalent BTK inhibitor?

John P. Leonard, MD:
Pirtobrutinib is approved for relapsed/refractory mantle cell lymphoma (MCL) after at least 2 lines of systemic therapy, including a BTK inhibitor. It is not yet approved in the upfront MCL setting, and there are currently no datasets to support its use as first-line therapy for MCL. Regarding the use of a covalent inhibitor following progression on pirtobrutinib, there is no clear evidence at this time that such a sequencing approach will be effective.

Ann S. LaCasce, MD, MMSc:
I agree. Although it is attractive to sequence pirtobrutinib prior to a covalent BTK inhibitor, we currently have no solid evidence to support this approach. Pirtobrutinib is certainly a well-tolerated drug, and it will be especially advantageous to older patients with MCL. Moreover, it is administered on a once-daily oral regimen, so it is convenient to use. On the phase I/II BRUIN trial, it demonstrated activity in 14 patients with covalent BTK inhibitor–naive MCL with an objective response rate of 85.7%. However, because this was seen in a very small patient population (N = 14), a larger study is needed to confirm and validate these results.

Matthew Lunning, DO, FACP:
I also agree. We need more solid evidence to support the use of pirtobrutinib prior to a covalent BTK inhibitor for patients with MCL.

What are your thoughts on the racial bias in clinical trials in oncology? 

John P. Leonard, MD:
It is increasingly becoming recognized that there are racial and socioeconomic disparities in the clinical trial system in the United States and, more broadly, in the healthcare care system worldwide. It is clear that some populations are underserved based on various socioeconomic factors. These disparities need to be addressed, and a more balanced inclusion of patients is required in clinical trials so that regardless of socioeconomic background or race, the results from the clinical trials are applicable to all patients who, ultimately, will receive these drugs when they are approved.

There is no doubt that the challenges faced regarding drug accessibility will vary by country and within each country, especially regarding the costs and affordability of the drugs. For unclear reasons, access to these novel BTK inhibitors, in particular, can be quite limited. It is my hope that with increasing awareness, the disparities in our healthcare system will significantly improve, because this is a challenge that needs to be rapidly addressed.

Your Thoughts?
What are the biggest challenges you experience in your practice when it comes to treating patients with MCL with a BTK inhibitor? Answer the polling question and join the conversation in the discussion box below.

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Have you incorporated pirtobrutinib into your practice for patients with MCL?

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