Predicting Outcomes for a Patient With Follicular Lymphoma

Christopher Flowers, MD: The typical age of onset of a patient with follicular lymphoma is in the late 60s or early 70s. This gentleman, who is in his 70s, is fairly typical of the type of patient we see. His initial disease behavior was fairly aggressive, with some symptoms—fevers as well as weight loss—at the time of his initial diagnosis. He was started on a standard chemoimmunotherapy regimen, R-CHOP [rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone], which in the United States, was one of the more commonly used chemoimmunotherapy regimens in years gone by.

There are now several other options available to patients, which would include bendamustine/rituximab or even lenalidomide/rituximab, which is yet another option for patients in the frontline setting.

What is reasonably concerning about this patient was that he had an early relapse of his disease, within 2 years of his initial diagnosis. About 20% of individuals with follicular lymphoma will have a relapse within 2 years of their diagnosis. When that happens, their expected outcomes are remarkably poorer than the standard patient with follicular lymphoma. When we see this, the kinds of things we think about are the potential or need for enrollment in a clinical trial, or even a combination chemoimmunotherapy regimen. We may potentially consider transplantation with an autologous stem cell transplant for younger individuals with follicular lymphoma.

Then, after his second relapse, the patient proceeded on to have a third relapse. Upon his third relapse, he was treated with an approved agent in that setting—a PI3-kinase inhibitor, idelalisib.

When we think about predicting outcomes for patients with follicular lymphoma, the FLIPI [Follicular Lymphoma International Prognostic Index] and FLIPI2 [Follicular Lymphoma International Prognostic Index 2] scores are now available to use as prognostic markers for patients. The FLIPI score consists of age, with the hallmark being age greater than 60; stage either III or IV; a hemoglobin of less than 12 [g/dL]; more than 4 nodal sites involved, with those nodal sites defined by FLIPI in terms of the nodal areas that need to be considered; and then also an elevated lactate dehydrogenase [LDH].

Our particular patient was an individual who was over the age of 60. He had stage IV disease. He had a low hemoglobin and had more than 4 nodal sites involved, as well as an elevated LDH. Therefore, he would fall into the FLIPI high-risk category. The FLIPI risk for each one of those factors scores as 1 point. FLIPI risk groups can be defined as low, intermediate, and high-risk groups. For those patients who fall into the FLIPI scores that have a low-risk group assigned to it, their expected 10-year overall survival is approximately 70%. For those who fall into the high-risk category, their expected overall survival at 10 years is about 35% or 36%. Clearly, very different outcomes for those 2 patient populations.

Like the FLIPI categories, FLIPI2 has been a prognostic scoring system that is a predictor of progression-free survival. It again uses the categories of age greater than 60, and hemoglobin, but substitutes additional categories—having a single lymph node that is bigger than 6 cm as that measure of bulk, having bone marrow involvement, and having an elevated beta2 microglobulin.

This patient had an elevated beta2 microglobulin and had bone marrow involvement, as well as was over the age of 60. His hemoglobin was less than 12 [g/dL]. So again, he would fall into the FLIPI2 poor-risk category, which is associated with worse outcomes.

Transcript edited for clarity.

Case:A 77-Year-Old Man With Follicular Lymphoma

Initial Presentation

• A 77-year-old man complains of a 4-month history of occasional fevers, decreased appetite, and an unintentional 7-lbs. weight loss
• PMH: unremarkable
• PE: palpable left axillary lymph nodes ~ 4 cm; spleen palpable 4.5 cm below costal margin
  
  

Clinical Work-up

• Labs: ANC 1.5 x 109/L, WBC 10.6 x 109/L, 42% lymphocytes, Hb 10.1 g/dL, plt 100 x 109/L, LDH 325 U/L, B2M 3.3 µg/mL; HBV negative
• Follicular lymphoma grade 2
• Bone marrow biopsy showed lymphoid aggregates, 35% involvement
• Molecular genetics: t(14;18) (q32;q21)
• PET/CT showed enlargement of left axillary, mediastinal and bilateral para-aortic lymphadenopathy (4.2 cm, 5.3 cm, 3.6 cm and 3.5 cm respectively)
• Ann Arbor Stage IV; ECOG 0
  
  

Treatment

• He was treated with R-CHOP for 6 cycles; continued rituximab maintenance 375 mg/m3; achieved partial response
• 6 months later he complained of increasing frequency of fevers
  • Repeat PET/CT revealed progression of disease
  • He was started on bendamustine + obinutuzumab for 6 cycles and continued maintenance obinutuzumab
  • Repeat lymph node biopsy grade 2 follicular lymphoma
• 8 months later he complained of increased weight loss
  • He was started on idelalisib 150 mg PO BID