A 45-Year-Old Woman with Newly Diagnosed Follicular Lymphoma - Episode 4

Newly Diagnosed Follicular Lymphoma: First-Line Anti-CD20 Therapy

The rationale for treating newly diagnosed follicular lymphoma with the anti-CD20 monoclonal antibody, obinutuzumab, in the first-line setting.

Daniel Greenwald, MD: CD20 is an attractive target for the treatment of lymphoma because it’s so highly expressed in lymphoma. We’ve known since the late 1990s that we can target CD20 using monoclonal antibodies except for normal B cells, which we acknowledge we will get rid of as we treat with an anti-CD20 antibody. This is a fairly specific treatment for lymphoma. We’ve also long recognized that there’s a synergy between treatment with the anti-CD20 antibodies and cytotoxic chemotherapy. I will often explain to patients that even though we’re suppressing their normal B cells, in most adults they can do well for a period of time without those B cells. There, of course, has to be vigilance for infection as there is an increased risk of opportunistic infections, but over the short-term, most adults will do well even when we target CD20. It has also been recognized that targeting CD20 can vary from 1 person to another. There are factors for the host or the patient’s immune system that influence the ability to respond to therapy against their lymphoma using an antibody. Newer generations of anti-CD20 antibodies have capitalized on our understanding of how the immune system functions. For example, newer versions may have an altered structure where they’re fully humanized rather than containing mouse components. They may have removal of sugar residues on the protein on the antibody, which enhances the immunologic function of the antibody. In other words, newer versions of anti-CD20 antibodies are engineered, we hope to work better and the clinical evidence has supported that.

The GALLIUM trial was a very large prospective study evaluating the treatment of frontline follicular lymphoma. This was a study of over 1200 patients and they were randomized to receive obinutuzumab [Gazyva] and chemotherapy vs rituximab [Rituxan] and chemotherapy, followed by respective maintenance schedules for each antibody. The treating oncologist could select the chemotherapy, but there was randomization to balance that factor. Many patients received bendamustine [Treanda], some patients CHOP [cyclophosphamide, doxorubicin, vincristine, and prednisone], some patients CVP [cyclophosphamide, vincristine, prednisone]. What it demonstrated was that there was a superior progression-free survival compared with rituximab chemotherapy, with medians not yet reached for either arm. The adverse events for obinutuzumab-based therapy are well described and can be mitigated with several measures. There was a slight increase in toxicity versus rituximab.

Transcript edited for clarity.

Case: A 45-Year-Old Woman with Follicular Lymphoma

Initial presentation

  • A 45-year-old woman presents with a 2-month history of fatigue and abdominal pain, enlarged lymph nodes in her right neck, and a 5-lb unintentional weight loss
  • PMH: Unremarkable
  • PE: right cervical and axillary lymph nodes palpated ~2 cm; spleen palpable 3 cm below left costal margin

Clinical workup

  • Labs: ANC 1.5 x 10^9, WBC 11.7 x 10^9, lymphocytes 41%, Hb 8.7 g/dL, plt 101 x10^9, LDH 305U/L, 3.6 B2M ug/mL; HBV negative
  • Excisional biopsy of cervical lymph node on IHC showed CD20+, CD10+, BCL2+, follicular lymphoma grade 2
  • Bone marrow biopsy showed paratrabecular lymphoid aggregates, 43% involvement
  • Cytogenetics: t(14:18) (q32;q21)
  • PET/CT showed right axillary, cervical, and mediastinal lymphadenopathy (2.7 cm, 2.5 cm, and 2.6 cm respectively)
  • Ann Arbor Stage IV, ECOG PS is 1

Treatment

  • Patient was treated with obinutuzumab plus bendamustine chemotherapy. She completed 6 cycles and treatment was well tolerated.
  • She continued on obinutuzumab maintenance.
  • 30 months later, she complains of fevers, chills, and decreased appetite.