Considerations for Therapy in R/R FL

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

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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: After patients complete their frontline or subsequent lines of therapy, they transition into active surveillance. There’s no good evidence as to the preferred strategy for active surveillance. Clinicians will often rely on guidelines from the NCCN [National Comprehensive Cancer Network] or their own SOPs [standard operating procedures] to derive how to pursue active surveillance. It is not unreasonable to assess patients every 3 to 6 months for a number of years and then transition to no more frequently than once a year. Whether to pursue active surveillance, meaning imaging studies or imaging modalities such as CT or PET [positron emission tomography], is not clearly defined. It is our common practice to pursue CT surveillance in the absence of concern for clinical transformation every 6 to 12 months. Once they get beyond 5 years, surveillance should be no more frequently than every 12 months.

There are other practices where they may not pursue any imaging modality in the absence of clinical concern for progressive disease. My only concern about that strategy is that at least half of patients will not have B symptoms. They may not have laboratory abnormalities, so you may be missing patients who are in need of therapy as a result of bulky or significant adenopathy that will only be picked up on an imaging study. I don’t advocate for CT scans every 6 months for patients who are looking at a natural life expectancy of about 18 to 20 years, but particularly in the first 5 years, routine surveillance imaging can be of benefit, mostly to identify patients with an early progression event.

Once patients get beyond that 24-month mark and are no longer concerned about being a patient with POD24 [progression of disease within 24 months], active surveillance can be performed based off of patient symptom burden, lab abnormalities that may be followed, and comfort level in terms of intervals. I frequently see patients every 12 months. In addition to being monitored for signs of recurrent follicular lymphoma, it’s also important to note that these patients are at higher risk for second cancers, so we’re also pursuing active survivorship, meaning ensuring they are up to date in terms of screening for other cancers. It’s important to ensure they’re up to date on mammograms, colonoscopies, and skin examinations. Basal cell and squamous cell carcinomas also occur more frequently in this patient population.

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