A 45-Year-Old Woman with Newly Diagnosed Follicular Lymphoma - Episode 2

Criteria Used in the Initial Diagnosis of Follicular Lymphoma

Recommendations for assessing and risk stratifying patients with newly diagnosed follicular lymphoma, with special considerations regarding the current role of molecular testing.

Daniel Greenwald, MD: For risk stratification, I follow current guidelines as well as get a general clinical assessment of the patient. The primary question always is, does this patient have symptoms or objective findings that would warrant treatment as opposed to expecting observation or as many of us call it, watch and wait? The other question is, are there features that concern occult transformation? This is an instance where a PET [positron emission tomography] scan can be quite helpful as was used in this case. And if there’s an area of intense FDG [fluorodeoxyglucose] uptake, where we suspect there may be transformation gene aggressive lymphoma, we’ll often pursue that with a biopsy to evaluate that. I do calculate the FLIPI [Follicular Lymphoma International Prognostic Index] because I think it’s helpful in understanding the burden of disease and the overall prognosis. And of course, that includes the age, the stage, the baseline hemoglobin, the DLDH [dihydrolipoamide dehydrogenase], and the number of noble sites. When deciding whether a patient needs treatment, we’re keen on their symptoms. Is there any obvious organ function that might be threatened, do they have cytopenias, do they have bulky disease, and are they progressing rapidly? When patients are considered for enrollment in clinical trials, we use objective criteria like the GELF [Groupe d'Etude des Lymphomes Folliculaires] criteria, which define bulk as 3 sites greater than 3 centimeters or a single site or more than 1 site greater than 7 centimeters, B symptoms splenomegaly, effusions, cytopenias, or leukemia. In this hypothetical case, the patient has several features that warrant initiation of therapy. We have learned from registration and observational studies that the FLIPI, while important, doesn’t tell the entire story. There are patients who can have a low FLIPI score who do poorly and patients who have a high or aggressive FLIPI score who may in fact do well. So there have been attempts at looking at other molecular measures, such as the TMTV [total metabolic tumor volume], the M7-FLIPI [M7-FLIPI incorporates the FLIPI score and mutational status from 7 genes], and other multigene models. But at the present time, I don’t use these in deciding initial therapy for patients with follicular lymphoma. As far as molecular features, I rely on the baseline and basic features that are required for diagnosis. This includes the hemostatic chemistry performed by the pathologist as well as translocation studies, and in some cases molecular studies to confirm we in fact have follicular lymphoma.

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.