Case Presentation: Relapsed/Refractory Follicular Lymphoma

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EP: 1.Case Presentation: Relapsed/Refractory Follicular Lymphoma

EP: 2.R/R FL Patient Case Review and Impressions

EP: 3.First-line Therapy Options in ND Follicular Lymphoma

EP: 4.Considerations for Therapy in R/R FL

EP: 5.Second-line Treatment Options for R/R FL Patients

EP: 6.Treatment Challenges Beyond the Second-line in R/R FL

EP: 7.Efficacy of tazemetostat in patients with EZH2m and EZH2wt R/R FL

EP: 8.Managing Side Effects of Tazemetostat in R/R FL

EP: 9.Future Directions and Unmet Needs in the Treatment of R/R FL

Loretta Nastoupil, MD: Hi, I’m Dr Loretta Nastoupil from the University of Texas MD Anderson Cancer Center. Today, I’ll be discussing a 75-year-old woman with relapsed/refractory follicular lymphoma. She has a 3-month history of fatigue, occasional fevers, decreased appetite, and an approximately 12-lb weight loss. Past medical history is notable for controlled hypertension, osteoporosis, and hyperlipidemia, which is managed with diet and exercise. On examination, she has palpable bilateral axillary and cervical nodes, approximately 3 cm in both axillae and 2 cm in the cervical nodes. Her spleen is palpable 4 cm below the left costal margin.

Further work-up included laboratory tests with an ANC [absolute neutrophil count] of 1.6 per mm3; total white blood cell count of 11.4 per mm3; hemoglobin of 9.8 g/dL; platelets were 98 per mm3; LDH [lactate dehydrogenase] of 325 U/L, which is higher than the upper limit of normal; beta-2 microglobulin was 3.7 μg/mL; and the hepatitis panel was negative. This patient underwent an excisional biopsy, revealing a CD20-positive, CD10-positive, and BCL2 grade 2 follicular lymphoma. A bone marrow biopsy was pursued to complete her staging work-up, revealing a paratrabecular lymphoid aggregate, 42% involved, with a phenotype consistent with follicular lymphoma. Cytogenetics reveal translocation (14;18). This patient also underwent molecular testing, revealing an EZH2 mutation. PET [positron emission tomography]/CT reveals the known bilateral axillary and left cervical adenopathy, as well as mediastinal adenopathy. The largest lymph node was 4.6 cm. This patient is stage IV, with an ECOG [performance status] of 1. For the FLIPI [Follicular Lymphoma International Prognostic Index] score, she has age, stage, hemoglobin, and LDH. It’s a FLIPI score of 4, so it’s a high-risk FLIPI case.

Her treatment history included bendamustine and rituximab times 6 cycles, and she achieved a partial response. She then pursued maintenance rituximab. Twenty-four months later, she complained of left upper quadrant discomfort, loss of appetite, fevers, and new onset pruritis that was insatiable. She was started on antibiotics, given concerns for potential infection contributing to her presenting symptoms. Without resolution of symptoms, imaging was pursued and a PET/CT revealed concerns for progressive disease. A biopsy was pursued and confirmed relapsed follicular lymphoma. She was then initiated on second-line therapy, which consisted of R-CHOP [rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone]. She completed 6 cycles and continued on maintenance for 2 years. Unfortunately, 12 months later, she had recurrence of these symptoms. Imaging was also worrisome for recurrent lymphoma. At this point, she was third line, and she initiated tazemetostat, 800 mg orally, twice daily.

To summarize, as a 75-year-old woman who presents with these symptoms and peripheral adenopathy, she has advanced stage disease and high-risk FLIPI. She completed 6 cycles of BR [bendamustine, rituximab]. She had a first recurrence. At that time, she was treated with R-CHOP [rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone]. There was a shorter remission duration, similar to what we know to be consistent in relapsed follicular lymphoma. In the third-line space, she was started on tazemetostat.

This transcript has been edited for clarity.

Case: A 75-Year-Old Woman With Relapsed/Refractory Follicular Lymphoma

Initial presentation

• A 75-year-old woman complains of a 3-month history of fatigue, occasional fevers, decreased appetite, fatigue, and a 12-lb weight loss
• PMH: Medically-controlled hypertension, osteoporosis, hypercholesterolemia managed with diet and exercise
• PE: palpable bilateral axillary and left cervical lymph nodes, ~ 3 cm in both axillae and 2 cm in the cervical nodes; spleen palpable 4 cm below left costal margin

Clinical workup

• Labs: ANC 1.6 x 109/L, WBC 11.4 x 109/L, 43% lymphocytes, Hb 9.8 g/dL, plt 98 x 109/L, LDH 325 U/L, B2M 3.7 µg/mL; HBV negative
• Excisional biopsy of the axillary lymph node on IHC showed CD 20+, CD 3+, CD5+, CD 10+, BCL2+; follicular lymphoma grade 2
• Bone marrow biopsy showed paratrabecular lymphoid aggregates, 42% involvement
• Cytogenetics: t(14;18) (q32;q21)
• Molecular testing: EZH2m+
• PET/CT showed bilateral axillary, left cervical, and mediastinal lymphadenopathy (3.3 cm, 3.1, cm and 4.6 cm respectively)
• Ann Arbor Stage IV; ECOG 1
   

Treatment

• She was treated with bendamustine and rituximab for 6 cycles, achieved partial response and continued rituximab maintenance
• 24 months later she complained of ULQ discomfort, loss of appetite, fevers new onset itching; she was currently taking antibiotics for her 2nd bacterial infection in the past 6 months
  • Repeat PET/CT revealed progression of disease
  • She was started on R-CHOP for 6 cycles and continued on rituximab maintenance
  • Repeat lymph node biopsy grade 2 follicular lymphoma
• 12 months later she complained of continued weight loss, increased itching and worsening fatigue; recurrent infections continued
  • She was started on tazemetostat 800 mg BID