Managing Early Progression in Follicular Lymphoma


Treatment options and variables that need to be considered when managing patients with follicular lymphoma who relapse early after first-line chemoimmunotherapy.

Daniel Greenwald, MD: To review our case, our patient achieved 30 months of freedom from trouble, as I say, but now she has relapsed after a cytotoxic chemotherapy and a monoclonal antibody. Considering that she was treated with maintenance therapy, it is suggested that she has a refractory to both of these modalities of therapy. In general, we don’t like to go back to a cytotoxic chemotherapy of the same mechanism that is close to the initial therapy, particularly 1 that can be harsh on the bone marrow, like bendamustine [Treanda]. It’s important to understand that not all patients with a relapse necessarily require treatment. Some can be monitored depending on the same factors that we considered during initial therapy. However, in this case, she’s having considerable symptoms. My first priority would be to establish whether there’s evidence of transformation. Again, repeating a PET [positron emission tomography] scan with a low threshold to rebiopsy an area of intense FDG [fluorodeoxyglucose] uptake. For the majority of patients, I look for an investigational protocol if 1 is available, and if it’s not available, I would certainly consider 1 of the many approved treatments utilized in the second-line setting. This might include lenalidomide [Revlimid] and rituximab [Rituxan], a PI3 [phosphoinositide 3] kinase inhibitor, or EZH2 [enhancer of zeste 2 polycomb repressive complex 2 subunit] inhibitor. Occasionally, I will use some of the older radiotherapies, but again, my focus is always looking for a clinical trial if available.

We know from lymphoma care and many registrational studies, as well as cohort studies, that patients who progress within 24 months of diagnosis tend to do more poorly. And that’s been supported by again, prospective studies following patients, but also retrospective analysis of patients undergoing therapy and study. Although this patient progressed at 30 months, it’s concerning that she’s progressed this early following this therapy and at this young age. It’s another reason to consider a full restaging, a full assessment for transformation, and, when indicated, assessment by a center with excellence for treatment in lymphoma that has access to not only investigational studies but, if necessary, cellular immunotherapy approaches, as well as a stem cell transplant.

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


  • 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.
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