Case Highlights: High-Risk Follicular Lymphoma

John Pagel, MD:This is a case of a 70-year-old gentleman who has a history of follicular lymphoma. It was diagnosed about 5 1/2 years ago when he presented with some adenopathy in his groin region. He has a history of hypertension but no other significant comorbidities. He had a presenting lymphocyte count that was in the normal range, and his bloodwork was also adequate, and he was followed for his grade 2 follicular lymphoma despite the fact that he had a high-risk FLIPI [Follicular Lymphoma International Prognostic Index] score and he had no evidence of transformation at the presentation. There were no indications for treatment, and so again he was followed for about 5 1/2 years. But the disease grew, and in fact he presented at that time with an 8 ½-centimeter mass in his abdomen and was treated with bendamustine/rituximab.

At that time of the route progression of his disease, his neutrophil count was about 1200. He was not anemic. His hemoglobin was almost 12, and his platelet count was around 105,000. Again, he had grade 2 follicular lymphoma with a high risk FLIPI score, but again without any evidence of transformation. As I said, he received bendamustine/rituximab. He received a full 6 cycles of therapy and achieved a partial remission that was durable for about 20 months. Unfortunately, after 20 months, his disease again progressed with an elevated LDH [lactate dehydrogenase] and recurrent adenopathy, and he was treated with rituximab and CHOP [R-CHOP; cyclophosphamide, doxorubicin, vincristine (Oncovin), and prednisone] chemoimmunotherapy.

He did achieve a partial remission after about the first 3 months of treatment, but unfortunately after 6 cycles of the R-CHOP, he only had a partial remission that lasted for about 5 months and showed disease progression. Because of the progressive disease after the R-CHOP, he was switched to oral idelalisib and oral PI3 kinase inhibitor, which is dosed at 100 mg twice a day.

Given the fact that this patient had a very large mass in his abdomen or retroperitoneum of about 8 1/2 centimeters, if he had significant symptoms related to that problem and there was concern about getting control of disease because of symptoms, I think radiotherapy could have been a reasonable option for control of that. However, there’s significant comorbidities that go along with radiation to the abdomen. So it’s probably not someone’s first choice of how they will approach this patient. Moreover, he had widespread disease at the time of relapse.

Radiotherapy is usually reserved for patients who have very localized disease, where in fact it’s going to be very well tolerated and likely not have specific problems related to the treatment. In general, however, with relapsed follicular lymphoma, it’s a systemic disease and it requires largely systemic therapy.

This patient unfortunately has a relatively aggressive disease, and we know that by the clinical picture. This patient relapsed within 2 years of getting frontline bendamustine/rituximab. That’s what we would call progression of disease at 24 months, or POD24. It’s based on some data from the National LymphoCare Study originally published, and now certainly confirmed by other groups, that show that if you relapse from up-front chemoimmunotherapy with your follicular lymphoma within 2 years, your chance for long-term survival is significantly limited.

In fact, 5-year survival rates are only on the order of about 50%. This is a high-risk patient population, and the specific patient population that we need to do better with. I might even point out, this is an exact example of where patients don’t do well after failing up-front chemoimmunotherapy, in this case, bendamustine/rituximab, and then go to some other chemotherapy regimen.In this case it was R-CHOP, and it didn’t do very much. So the idea of switching therapies and moving on to something like idelalisib, with a different mechanism of action of cell killing, certainly has significant rationale.

Transcript edited for clarity.

Case:A 70-Year-Old Man With Follicular Lymphoma

H & P:

• A 70-year-old man presents with night sweats and general fatigue
• PMH: hypertension, no history of MACE
• PE: Groin is tender to touch, no tenderness in abdomen
• Initially diagnosed with bilateral axillary contiguous stage II FL 5.5 years ago
  • Grade 2 FL, 4 masses (each >3 cm)
  • FLIPI status: high risk

Current biopsy and labs:

• Biopsy: grade 2 FL without transformation
• ECOG performance status: 1
• Hematologic results
  • ANL: 1200 /µL
  • Platelets: 105,000 /µL
  • Hemoglobin: 11.9 g/dL
• LDH: 335 U/L
• eGFR: 75 mL/min/1.73²
• Imaging: PET/CT reveals inguinal lymphadenopathy, with largest mass 8.5 cm

Treatment and disease history

• Front-line BR
  • Completed 6 cycles, achieved PR by 3 months
  • Maintained PR for 20 months before developing fever and mediastinal lymphadenopahty
• Second-line R-CHOP
  • Competed 6 cycles, achieved PR at 3 months
  • PR maintained for 5 months
  • Time since completion of last treatment: 5 months

Current treatment

• Started on single-agent idelalisib 150 mg twice a day