Follicular Lymphoma: Treating Early Progression

Ajay K. Gopal, MD: Again, this patient had a relatively short initial remission duration. The patient falls into about the 20% range of patients who have early progression. Fortunately, the patient did not have evidence of histologic transformation. Nevertheless, this is still a fairly poor prognosis group, even if you take out the transformed patients. The question here really is, what do you do? Most people, including myself, try to do something other than chemoimmunotherapy when we see a patient with early progression. I will concede that the data are not available as to what the right answer is, but more of the same treatment is probably not the right answer, unless maybe you’re using chemotherapy as a stepping-stone to something more definitive. The more definitive thing might be something like an autologous transplant. This patient, based on age, might be borderline regarding their candidacy for an autotransplant. There can be very fit 69-year-olds, and age is not a strict exclusion, but nevertheless, this patient might be in the upper limit of age for an autologous transplant.

If I’m not using a chemoimmunotherapy approach, I would typically try to do something that’s different. Thankfully, we now have some other, different options. One option is the combination of lenalidomide/rituximab. In a comparative trial to rituximab alone, that combination showed a significant benefit in progression-free survival. Now, the major caveat to those data is that was a rituximab-sensitive patient population. This patient is not rituximab-sensitive. The patient progressed on rituximab maintenance. And so, I think we would expect our results to be inferior to what we’ve seen in the AUGMENT study.

Another approved agent is ibritumomab tiuxetan. This is a radioimmunoconjugate, a single infusion, for patients who have low bone marrow involvement. It can be quite effective and has very low toxicity in the second-line setting, particularly for older patients.

I really try to think about clinical trials for these patients, however, and this is the exact type of patient I would refer to a major center for a clinical trial.

Transcript edited for clarity.

Case:A 69-Year-Old Woman With Follicular Lymphoma

Initial Presentation

• A 69-year-old woman complains of a 5-month history of fatigue, decreased appetite and a 10-bs. weight loss
• PMH: unremarkable
• PE: right axillary and bilateral cervical lymph nodes palpated ~ 3 cm; spleen palpable 4 cm below costal margin
  
  

Clinical Work-up

• Labs: ANC 1.6 x 109/L, WBC 11.8 x 109/L, 40% lymphocytes, Hb 8.9 g/dL, plt 98 x 109/L, LDH 308 U/L, B2M 3.7 µg/mL; HBV negative
• Excisional biopsy of the lymph node on IHC showed CD 20+, CD 10+, BCL2+; follicular lymphoma grade 2
• Bone marrow biopsy showed paratrabecular lymphoid aggregates, 45% involvement
• Molecular genetics: t(14;18) (q32;q21)
• PET/CT showed enlargement of right axillary lymph nodes (3.1 cm, 3.2 cm), diffusely enlarged nodes in the retroperitoneal and lumbar lymph nodes
• Ann Arbor Stage IV; ECOG 1
  
  

Treatment

• She was treated with R-CHOP for 6 cycles with rituximab maintenance; achieved partial response
• 5 months later she complained of increasing fatigue
  • Repeat PET/CT revealed progression of disease
  • She was started on bendamustine + obinutuzumab for 6 cycles and continued maintenance obinutuzumab
  • Repeat lymph node biopsy remained grade 1-2 follicular lymphoma
• 9 months later she complained of chills and low-grade fever
  • She was started on idelalisib 150 mg PO BID