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Marginal Zone Lymphoma Case Studies

MZL: Managing Patients Who Receive Ibrutinib

Ariela Noy, MD
Published Online:Aug 27, 2018
Ariela Noy, MD, discusses the rationale for treating a 64-year-old woman with advanced extranodal marginal zone lymphoma (MZL) with ibrutinib after rituximab therapy and disease progression.

Second-Line Therapy in Extranodal Marginal Zone Lymphoma


Ariela Noy, MD: Physicians ask about the adverse event profile of ibrutinib in comparison to other options for the treatment of relapsed/refractory MZL. We do not have a direct comparison trial. That would be the definitive answer to that question. However, we can compare the results of the Pharmacyclics PCYC-1121-CA trial to other trials, to trials of indolent lymphoma that included marginal zone lymphoma or trials that looked at follicular lymphoma patients alone. Generally, the adverse event profile seems favorable for ibrutinib. Specifically, the toxicities are typically grade 1 or grade 2. They are very rarely grade 3 or grade 4. It’s highly unusual that a patient would die on ibrutinib therapy of causes that are related to treatment. In addition, dose modification of ibrutinib allows patients to continue therapy even if they’ve had a grade 3 or grade 4 event.

One of the important questions is whether atrial fibrillation and its risks, secondary to ibrutinib, are an important issue. The actual risk of atrial fibrillation is probably cumulative and can occur later into the treatment—as much as several months into therapy. Patients do have the option to continue ibrutinib with correct and careful management of their atrial fibrillation. In fact, treatment paradigms have been published on the use of anticoagulants and the various forms of treatment for atrial fibrillation. Happily, a patient who is doing well on ibrutinib can, therefore, continue ibrutinib with atrial fibrillation management.

Another common question is, what is the adverse event profile regarding bleeding? Because of nontargeted effects in platelets, patients can develop bleeding. Most of the bleeding is quite superficial and manageable. Typically, we see light bruising, most commonly on the upper extremities. With counseling, patients are comfortable with that. The more concerning profile is in regard to severe adverse event bleeding. It’s actually relatively rare with ibrutinib. We counsel patients on the risks of surgery to avoid any complications, and the FDA has included directions for simple and more complicated procedures in the package labeling.

In addition, on the Pharmacyclics PCYC-1121-CA trial, only 1 person had a severe event, in terms of intracranial bleeding. That patient had not taken the drug for a substantial number of days, so the bleeding was not related to ibrutinib.

I’ve treated a lot of patients with marginal zone lymphoma over the years, and I’m happy to say that patients are doing very well right now. Having a new treatment option that is not chemotherapy-related has made an impact on a lot of patients’ lives. Those patients really appreciate having a good quality of life, concurrently with disease control, so that they can lead normal lives.

Transcript edited for clarity.

A 64-Year-Old Woman With Advanced Extranodal MZL

January 2016

  • PH: At age 64, the patient presented with a fever of unknown origin, weight loss, and fatigue
    • PE: revealed 2 masses near left ear
    • PMH: Sjogren’s syndrome, symptoms managed on cevimeline
  • CT revealed bilateral involvement in parotid glands and a 3.0-cm. mass in the left lung
  • Biopsies confirmed presence of MALT lymphoma in salivary gland and lung with nodules of diffuse heterogeneous B-cell infiltrate
  • IHC: B cell phenotype CD20
  • HBC, HBV, and other infections ruled out

Treatment History

  • After 6-month period of active monitoring/observation, salivary masses began to cause patient distress; she also developed a persistent cough
    • CT revealed an additional new mass in left lung
  • Decision was made to start patient on a course of rituximab
  • Follow-up imaging at 6 months and 9 months showed near complete remission

March 2018

  • Imaging at 20 months showed disease progression in the lung  
  • Patient started on treatment with rituximab monotherapy

June 2018

  • Imaging at 3 months showed no response to therapy
  • The patient was started on treatment with ibrutinib
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