Anti-CD20 Antibody Therapy in First-Line MZL

John N. Allan, MD:When we’re thinking about treatment with single-agent anti-CD20 antibodies such as rituximab versus chemoimmunotherapy approaches such as bendamustine/rituximab or R-CHOP, we look at whether or not the patient is symptomatic. What are their comorbidities? What are their treatment goals? Do they want to avoid more aggressive regimens? We really have to make it a patient-centered decision.

If they are older and have more comorbidities, I feel more comfortable backing off and using single-agent anti-CD20 therapy. Additionally, if they have low burden but are somewhat symptomatic, and we’re potentially trying to prevent needing to use more chemoimmunotherapy, and if we simply observe and the lymph nodes grow to be bulkier—more than 5 cm; closer to 7 cm—I may decide to treat with anti-CD20 therapy to try to capture the patient in a low tumor burden situation.

When a patient is symptomatic, when they have bulky adenopathy, and when they are in need of a response that’s going to be more rapid and durable, I start to think of our acute chemoimmunotherapy options.

When we’re looking at which type of anti-CD20 therapy we want to use, we are fortunate to now have several antibodies currently FDA approved for different indications. Although there’s not currently an FDA approval for third-generation antibodies such as obinutuzumab, we are able to access these drugs because the marginal zone lymphomas have been studied in randomized phase III protocols. In an up-front setting, I typically don’t use obinutuzumab. I’ll typically use rituximab. But in a second-line setting or in any patient who demonstrates that they are rituximab refractory, I will employ…something that is potentially considered to be a better or more effective antibody and may use obinutuzumab.

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