Follicular Lymphoma: Prognostic Scoring and Treatment Decisions

Ajay K. Gopal, MD: Clearly, this is a high-risk follicular lymphoma case. This is a patient who had early relapse after R-CHOP [rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone] chemotherapy, and had a very short remission duration after second-line chemoimmunotherapy. We can look a little bit at the prognostic factors. If we try to glean the FLIPI [Follicular Lymphoma International Prognostic Index] score from this case, likely a score of 5—age, stage, hemoglobin, extra nodal sites, and LDH [lactate dehydrogenase]—we would expect about a 35% 10-year overall survival in this situation. There is another FLIPI categorization called FLIPI2 that takes into account beta2 microglobulin and marrow involvement. So she probably had a FLIPI2 score of 4 here, which would have given her about a 20% 5-year overall survival. Both of these are relatively high-risk from the start.

However, the FLIPI and FLIPI2 scores don’t necessarily drive us to choose 1 therapy over another. The scores just give us a general idea of prognosis. She had a very appropriate treatment. I suspect rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone was chosen potentially because her disease was behaving badly, and she may have had some symptoms that might have worried the treating physician about some occult transformation. So she received rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone, but unfortunately had a very short remission after that.

This patient falls into this category of progression of disease by 24 months, and it’s been looked at by a number of groups. Really, not surprisingly, early progression portends a very poor outcome.

An important point from this case is that the treating physician was very diligent and performed a repeat biopsy. The thing to remember with early progression is there is a high rate of transformation. If you look at the PRIMA data, 37% of the patients who had progression within 1 year actually had evidence of histologic transformation to diffuse large B-cell lymphoma. If we look at the BC Cancer agency data of patients treated after bendamustine/rituximab, those who progressed within 2 years had a 76% rate of histologic transformation. So it is very important, in terms of management, to make sure you repeatedly biopsy patients with an early relapse. Our practice is, whenever possible, we want to make sure we know what we’re dealing with when we are changing from one therapy to another. This physician did the right thing. The physician did a biopsy, did not see evidence of early transformation, and saw, still, persistent follicular lymphoma and went on to a second-line regimen.

Now, I think the bigger question in this situation is, should one go with a chemoimmunotherapy-based regimen when you’ve already had a short remission after prior chemotherapy? I think that’s a matter of debate. Bendamustine/obinutuzumab is an approved approach, particularly for those with rituximab-refractory disease. But unfortunately, this patient did not get much of a remission after the bendamustine/obinutuzumab strategy.

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