Case Overview: Advanced MZL With Disease Progression

John N. Allan, MD:This is the case of a 65-year-old gentleman who was diagnosed with a nodal marginal zone lymphoma in November of 2014. When he presented, he presented with diffuse adenopathy. He came to his doctor because of lymph nodes in his groin. Upon initial exam, his physician found that he had diffuse adenopathy not just in his groin but also in his axilla—in his right axilla, as well as in the bilateral groin. Overall, he was noted to feel generally well, without too many symptoms. His past medical history was negative for any significant medical conditions, such as cardiovascular disease or diabetes. He was an otherwise generally healthy gentleman.

Upon initial lab work, he was found to be negative for HIV. He was also negative for hepatitis C and hepatitis B. Initial lab work showed a mild neutropenia—about 900 ANC. No other significant or major abnormalities showed up on his blood work.

He was recommended for a biopsy, at which point biopsies of the groin node revealed that it was a B-cell malignancy. It really just expressed CD19 and CD20 and was negative for other common markers that were evaluated. Baseline imaging revealed diffuse adenopathy, as well. That was confirmed in multiple nodal sites, but it was noted that most of these nodal sites were less than 2 cm. Given that he was feeling well, the recommendation from his physician was to continue to monitor him and observe him with physical exams and imaging going forward.

In November of 2015, he was noted to have disease progression. He felt lymph nodes growing in his arms, axilla, and groin. At that point, his physician had discussions with him about treatment options. The decision to initiate chemoimmunotherapy with bendamustine and rituximab was made.

The patient did relatively well. He had a decent response. Unfortunately, 2 years later, he did have a relapse. Again, he was noted to have enlarging lymphadenopathy. Given that he had relapsed in a short amount of time, within about 2 years, it was decided not to rechallenge him with bendamustine/rituximab. His physician recommended a more aggressive regimen—R-CHOP.

He received all 6 cycles of R-CHOP. At the end of treatment, he was noted to only have a partial remission. At that point, given that he’d just gotten chemotherapy, was in a remission, and was feeling a little better, he was recommended for observation. Unfortunately, this remission was also shorter than the previous one. Seven months later, he came back to his physician and, again, noted disease progression with enlarged lymphadenopathy and a return of symptoms of fatigue.

At this point, the patient and his physician had several decisions to make. The recommendation was to initiate third-line treatment with a drug called ibrutinib. The drug was initiated. He tolerated it relatively well but had some complications with diarrhea that resolved with over-the-counter therapy. He had noticeable bruising throughout the treatment but no significant major bleeding. His course was complicated by neutropenia, at which point the drug had to be held. The neutropenia resolved within a short amount of time, and then he was rechallenged at the same dose. The patient continues on this therapy.

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