Using Ibrutinib in Relapsed/Refractory MZL

John N. Allan, MD:When we’re thinking about a patient who might be eligible for ibrutinib-based treatment, we really take some patient considerations into account. Overall, the drug is well tolerated. There are some complications that are associated with it that should be recognized. Some of the major complications that we note with this drug are atrial fibrillation—AFIB—which is noted in 10% to 15% of patients in quoted studies, as well as bleeding. It has an antiplatelet effect that is similar to aspirin. Patients may have bruising, and significant bleeds have also been noted, although at very low percentages.

Bruising and AFIB are the major things that we think about. If we have an older patient with cardiovascular disease, who might already have AFIB and might be on a blood thinner and is a fall-risk patient, you have to take that into consideration when you’re considering initiating ibrutinib. Otherwise, if the patient is relatively healthy or relatively robust, ibrutinib is a very good option. It’s well tolerated and can be used safely and effectively.

That’s not to say that if there are complications in a patient who has comorbidities of AFIB or cardiovascular disease that this drug cannot be used. It absolutely can be used, and we use it in the clinic and in practice. For these patients, you just have to consider potential alternatives if you potentially see that they may not tolerate the drug well.

When managing toxicities of ibrutinib, you really have to be aware of what the symptoms of AFIB are. Many times, patients will talk about palpitations and fluttering and things like that. When you talk to them, it’s very brief. And so, it’s kind of hard to decipher. So, when your patient is on these types of drugs, any of those types of complaints need to be taken very seriously. At that point, you need to do your workup appropriately, do EKGs, and monitor and ask about them. Sometimes patients aren’t so forthright in bringing up their symptoms. Ask about bleeding. Ask about diarrhea. Ask about joint aches. You really have to monitor them. You really need to inquire about these types of things. Typically, we’re seeing patients on an every-couple-of months basis or so. When they come back, these are the things to be aware of—to look for and discuss with the patient. I try to identify these things before they become more problematic and/or uncontrolled.

Transcript edited for clarity.

A 65-Year-Old Man With Advanced Nodal MZL

November 2014

History & Physical:

• A 65-year-old man presented with multiple lumps in groin, no pain
• PMH: negative for HCV, HBV, HIV
• PE: marked swelling in right axillary and bilateral inguinal lymph nodes
  • ECOG performance status: 0
  • Otherwise healthy, no history of CV disease or diabetes, weight within normal range
• CT revealed lymphadenopathy at multiple nodal sites with multiple involved nodes (each <2 cm) involved at each site; no extranodal involvement or bulky disease
• Biopsies confirmed presence of B cell infiltrate
• IHC: B cell phenotype CD20, CD19

Treatment History:

• He was started on active monitoring with CT, histology, and pathology every 6 mo.

November 2015

• At 12 months following diagnosis, disease progression was shown on imaging, with additional involved axillary nodes
• The patient was started on treatment with bendamustine/rituximab (BR)

November 2017

• Follow-up imaging at 2 years following initiation of BR revealed disease progression in multiple lymph nodes at several sites
  • 2 nodes measuring >3.0 cm
• The patient was started on R-CHOP; he achieved a partial response

June 2018

• 7 months later, the patient developed relapsed disease
• He was started on treatment with ibrutinib 560 mg/day orally
  • He developed mild diarrhea (managed with OTC anti-diarrheal) and bruising on legs from minor bumps
  • Follow-up CBC showed grade 3 neutropenia without fever
• Ibrutinib was discontinued until neutrophils recovered and restarted at same dose without incident