Prognostic Evaluation for Treatment of FL

Nathan H. Fowler, MD:Today, the scoring systems or the prognostic systems for follicular lymphoma are in the state of evolution. In the past, we used the IPI, or International Prognostic Index, to score follicular lymphomas. Several years ago, we modified that to create the FLIPI scoring system, or the Follicular Lymphoma International Prognostic Index. The Follicular Lymphoma International Prognostic Index, or the FLIPI, includes 5 factors: age, stage, number of nodal sites, the LDH above normal, as well as anemia.

In patients who have basically different numbers of these FLIPI factors, we then can put them into different cohorts and estimate their 10-year overall survival. The problem with the FLIPI scoring system along with the IPI is that they really only predict the outcomes of a group of patients. And what I mean by that is that patients can have a high-risk FLIPI score but still do very well. And there are some patients who can have very low-risk FLIPI scores and do very poorly. So, again, it predicts the outcomes of an entire group, but there are many times individuals within that group can do good or bad regardless of their FLIPI score. So, in practice, I generally don’t use this to stratify patients in the different types of therapy. I do think it’s a useful tool to help us maybe understand how a patient could do and maybe decide how to follow them after treatment. But I don’t think that it’s currently, or should be currently, used to determine different types of treatment.

One of the first questions when you see a patient in clinic is, do they require treatment? In this patient, I feel they do require treatment. And that’s because she has symptoms. As we mentioned, she has cervical nodes that she can palpate. She has splenomegaly, but she also has night sweats. We do have several modified systems that can help us determine who needs treatment.

I generally think of 5 factors when determining whether patients need treatment. No. 1, if they’re symptomatic. No. 2, if they have enlarged spleen. No. 3, if they have anemia or cytopenias that are due to the disease. No. 4, if they have threatened organ function. And that usually means that regardless of the size of the node, it’s pressing on a critical structure, and often that can be something like the ureter. So, even if the node is small, if it’s pressing on a ureter and the patient is at risk for hydronecrosis, we start them on treatment.

And the final factor would be bulk. And that would mean to me, generally, lymph nodes that are above 5 cm or 6 cm. There are other scoring systems like the GELF, which is a French scoring system for high tumor burden. And there they define bulk as 3 nodes more than 3 cm or 1 node more than 7 cm. So, when I’m seeing patients in clinic, I’m going through my head and determining whether their clinical picture fits one of these criteria. And if they do, I generally start treatment.

Transcript edited for clarity.

June 2015

• A 65-year old female presented to her PCP complaining of night sweats and swelling in the neck
• PMH: osteoporosis, neurogenic bladder
• Physical examination:
  • Enlarged spleen 2 cm. below costal margin, bilateral cervical and axillary lymphadenopathy
• ECOG 0
• Laboratory findings:
  • WBC: 12 x 10⁹/L; 45% lymphocytes
  • Hb: 11.5 g/dL
  • Platelets: 213 x 10⁹/L
  • LDH 212 U/L
• Excisional biopsy of the lymph nodes:
  • IHC: CD10+, BCL2+
  • Follicular lymphoma, grade IIIa
• Bone marrow biopsy, 40% involved
• ¹⁸FDG-PET showed SUVmax of 9 with discrete masses bilaterally in the cervical and axillary region and increased uptake in the liver
• FLIPI 4 points, high risk
• The patient was started on bendamustine + rituximab (6 cycles) and was continued on rituximab maintenance therapy for 12 months
• She achieved a partial response with a 75% reduction in tumor volume

February 2018

• After 32 months, the patient complained of her symptoms returning
• CT showed disease progression in the axillary and hilar lymph nodes
• PET with SUV of 11
• Re-biopsy of lymph node, consistent with follicular lymphoma grade IIIa
• The patient was referred to an academic center for treatment
• She was enrolled in an open-label clinical trial of lenalidomide/rituximab (12 cycles)
• She achieved partial remission after 3 months

February 2019

• Twelve months later, the patient presents with low-grade fever and chills, she is otherwise well-appearing and continues to exercise regularly
• ECOG 0
• PET-CT showed further progression in the axillary lymph nodes
• The patient was treated with IV copanlisib and achieved a partial response after 4 cycles; she continues to do well on therapy