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FAQs: Role of BTKis in MCL

CE / CME

FAQs: Current and Emerging Roles of BTK Inhibitors in MCL

Physicians: maximum of 0.25 AMA PRA Category 1 CreditTM

Pharmacists: 0.25 contact hour (0.025 CEUs)

Registered Nurses: 0.25 Nursing contact hour and 0.2 pharmacology credits

Released: October 19, 2023

Expiration: October 18, 2024

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Key Takeaways
  • For patients with MCL and TP53 mutations, experts do not recommend intensive chemotherapy but rather a chemotherapy-free therapeutic approach.
  • Acalabrutinib-associated headaches are very manageable and tend to improve over time.
  • The new noncovalent BTK inhibitor pirtobrutinib is well tolerated.

In this commentary, Julie M. Vose, MD, MBA, and Brad Kahl, MD, address clinical questions posed by the audience during the recent symposium titled “Mantle Cell Lymphoma: Novel Therapeutic Strategies Using the New Generation of BTK Inhibitors” held during the SOHO 2023 annual meeting.

How would you treat a patient with blastoid mantle cell lymphoma (MCL) in the frontline setting?

Brad Kahl, MD:
I think one of the things to figure out right away is if the patient’s disease harbors a TP53 mutation or not. Often, blastoid morphology and the presence of TP53 mutations occur simultaneously in MCL. If the disease is TP53 mutated, I would not recommend the use of intensive chemotherapy. Patients with TP53 mutations are likely better served by a chemotherapy-free strategy. If the disease has blastoid morphology and does not harbor TP53 mutations, I would recommend intensive therapy with high‑dose cytarabine followed by autologous stem cell transplant. A good clinical outcome may still be achieved in a patient with blastoid morphology without TP53 mutations.

Julie M. Vose, MD, MBA:
I agree. The use of intensive therapy becomes more of an issue if the patient is older and is unable to tolerate a high‑dose cytarabine-containing regimen. In such a patient, the treatment approach is less clear because bendamustine plus rituximab does not generate a good response in this setting.

Brad Kahl, MD:
This is correct. Bendamustine generates disappointing outcomes among patients with highly proliferative disease. I have used rituximab plus cyclophosphamide/doxorubicin/vincristine/prednisone on occasion and I have also used the rituximab plus bendamustine/cytarabine (R‑BAC) regimen, which contains a lower‑dose of bendamustine and a lower‑dose of cytarabine. For older patients with highly proliferative MCL, I have had pretty good results with R‑BAC.

Dr. Vose, what have you tried in older patients with such proliferative disease?

Julie M. Vose, MD, MBA:
I have tried the R‑BAC regimen, but even that is a little bit tough for some of these older patients. It is a difficult situation with an answer that is not so clear at the moment. Overall, if a BTK inhibitor can be used upfront, I think for that type of patient, it would be extremely helpful.

Do you have any experience with the BOVen regimen of zanubrutinib, obinutuzumab, and venetoclax for patients with MCL? 

Brad Kahl, MD:
Yes, I do. This is a really interesting regimen, and Memorial Sloan Kettering Cancer Center is currently conducting an ongoing phase II clinical trial using this regimen (NCT03824483). I have used BOVen‑like regimens for patients with TP53‑mutated MCL in the relapsed/refractory setting, but I do not have any frontline experience with it. Nonetheless, I think a regimen like that could turn out to be a great option for patients with TP53-mutated MCL especially, and it may turn out to be a great treatment option for all patients with MCL. We need more data from clinical trials to support its efficacy and safety in MCL.

Julie M. Vose, MD, MBA:
I agree. The results from the ongoing phase II trial of BOVen in MCL will be enlightening and interesting.

What is the best approach to managing headaches associated with acalabrutinib?

Julie M. Vose, MD, MBA:
Headaches resulting from the use of acalabrutinib usually occur soon after starting the drug and seem to improve with time. Treatments to manage this adverse event include acetaminophen or forms of caffeine.

Brad Kahl, MD:
I recommend that my patients drink coffee, tea, or some other caffeinated beverage. Typically, acalabrutinib-associated headaches respond well to this management strategy. In addition, the headaches tend to dissipate over time and become less of an issue.

How would you treat an older patient with comorbidities and relapsed/refractory MCL after receiving frontline bendamustine/rituximab followed by maintenance rituximab and second-line zanubrutinib? 

Brad Kahl, MD:
Even though I do not have a lot of experience with the noncovalent BTK inhibitor pirtobrutinib, I know that it is definitely very well tolerated. For those patients in their 80s with comorbidities making them ineligible candidates for CAR T‑cell therapy, I will definitely recommend pirtobrutinib first.

Julie M. Vose, MD, MBA:
I agree. If a patient is a candidate for CAR T-cell therapy, I would try that first if I think it is safe enough for the patient. However, CAR T-cell therapy can be a pretty rough treatment for patients in their 70s, and certainly for those in their 80s. For older patients with MCL, especially those in their 80s, I would recommend pirtobrutinib rather than CAR T-cell therapy.

 

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In your practice, have you recommended a BTK inhibitor as frontline therapy for patients with MCL?

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