A 74-Year-Old Man With Relapsed/Refractory Follicular Lymphoma - Episode 1

Case Presentation: 74-Year-Old Man With Relapsed/Refractory Follicular Lymphoma

Kami Maddocks, MD, presents the patient diagnosis and treatment history of a 74-year-old-man with relapsed/refractory follicular lymphoma.

Kami Maddocks, MD: Hello, my name is Kami Maddocks from The Ohio State University James Cancer Center. Today, we’re going to discuss a case of follicular lymphoma [FL]. A 74-year-old man presents with complaints of a 6-month history of fatigue, fevers, anorexia, and an 8-pound weight loss. His past medical history is unremarkable. On a physical exam, he’s noted to have bilateral cervical lymphadenopathy, right axillary lymphadenopathy with the largest palpable node being about 3 centimeters [cm], and his spleen is palpable about 4.5 cm below the margin.

He has workup with labs and scans. His labs show a hemoglobin of 9.6, a white [blood cell] count of 11.2, platelets of 98,000 and LDH [lactate dehydrogenase] is elevated at 315, beta-2 microglobulin is elevated, hepatitis and HIV [human immunodeficiency virus] studies are negative. He’s referred for a PET [positron emission tomography] CT [computed tomography] scan which shows right axillary cervical and mediastinal lymphadenopathy with 3.3, 3.1, and 4.6 cm lymph nodes. He’s referred for an excisional lymph node biopsy. They excise the right axillary lymph node which shows CD20, CD10, ECL2 positive cells, consistent with a grade 2 follicular lymphoma.

Bone marrow shows low level involvement with FL, and FISH [fluorescence in situ hybridization] shows translocation (14;18) consistent with FL. He’s staged at Ann Arbor [University of Michigan Hospital] stage IV with an ECOG [Eastern Cooperative Oncology Group] performance status of 0. He undergoes treatment for his FL. He is initially treated with rituximab in combination with CHOP [cyclophosphamide, doxorubicin hydrochloride (hydroxydaunorubicin), vincristine sulfate (Oncovin), and prednisone] chemotherapy for 6 cycles and achieves a complete response to this therapy. He is then continued rituximab maintenance. 24 months after completing his initial chemotherapy, he again complains of symptoms of weight loss, fever, and drenching night sweats, as well as fatigue and pruritus. He has a repeat PET scan which reveals progression of his disease. He’s started on further therapy with bendamustine in combination with rituximab for 6 cycles, and then again is started on rituximab maintenance.

12 months later, he complains of continued weight loss with increased pruritus and fatigue. He has a biopsy which confirms grade 2 FL, and he’s started on treatment with idelalisib at 150 milligrams [mg] orally twice daily.

When we look at this case, we have a 74-year-old male who presents with these symptoms and palpable adenopathy. Presentation for follicular can be a few different things. Some patients present with asymptomatic disease found incidentally when they’re being worked up for other symptoms. Other patients will present with palpable lymphadenopathy, and a small proportion of patients will have these symptoms like this patient.

The average age of a patient presenting with follicular lymphoma is in their 60s, so this patient is a little bit older than that, but we do see several patients in this age range. When patients present with symptomatic disease requiring treatment, they often will have lymph node involvement, cytopenias from their disease and bone marrow involvement also.

When we look at prognosis for FL, there’s a few things that we can look at. We evaluate prognosis initially based on different risk scores, the most common which is the Follicular Lymphoma International Prognostic Index [FLIPI]. The FLIPI has 5 clinical risk factors, which include age greater than 60, stage III or IV disease, an elevated LDH, hemoglobin less than 12, and nodal sites greater than four. There are other risk factors such as the FLIPI2 or the PRIMA [PRIMA-PI] risk score, which also combined clinical risk factors to help define both progression- free survival from therapy and overall survival [OS] in general. This patient based on his clinical presentation would be considered to have both high-risk disease by FLIPI and FLIPI2 scores. Currently, we use those for prognostication, but we don’t use those to choose therapy.

Another thing about this patient in his prognostication is just looking at his response to treatment. One of the most prognostic things in FL is a patient’s initial response to their therapy. We know that patients who progress in 22 years, which is 24 or less months after their initial treatment, that they have a worse prognosis overall. We know that their 5-year OS is only about 50% compared with being 90% of those patients who retain their remission at 2 years. While this is not something you know when you start treatment, we do know that those patients who have early relapses have a lower OS, which would be the case with this patient.

Transcript edited for clarity.


Case: A 74-Year-Old Man With Relapsed/Refractory Follicular Lymphoma

Initial presentation

  • A 74-year-old man complains of a 6-month history of fatigue, occasional fevers, decreased appetite, fatigue, and an 8-lb weight loss
  • PMH: unremarkable
  • PE: palpable right axillary and cervical lymph nodes, palpable ~ 3 cm in both locations; spleen palpable 4.5 cm below left costal margin
     

Clinical Workup

  • Labs: ANC 1.6 x 109/L, WBC 11.2 x 109/L, 44% lymphocytes, Hb 9.6 g/dL, plt 98 x 109/L, LDH 315 U/L, B2M 3.5 µg/mL; HBV negative
  • Excisional biopsy of the axillary lymph node on IHC showed CD 20+, CD 3+, CD5+, CD 10+, BCL2+; follicular lymphoma grade 2
  • Bone marrow biopsy showed paratrabecular lymphoid aggregates, 4% involvement
  • Molecular genetics: t(14;18) (q32;q21)
  • PET/CT showed enlargement of right axillary, cervical, and mediastinal lymphadenopathy (3.3 cm, 3.1, cm and 4.6 cm respectively)
  • Ann Arbor Stage IV; ECOG 0
     

Treatment

  • He was treated with R-CHOP for 6 cycles, achieved complete response and continued rituximab maintenance
  • 24 months later he complained of increasing weight loss, fever and drenching sweats as well as more enduring fatigue and new onset itching; he was currently taking antibiotics for his 3rd bacterial infection in the past year
    • Repeat PET/CT revealed progression of disease
    • He was started on bendamustine + rituximab for 6 cycles and continued on rituximab maintenance
    • Repeat lymph node biopsy grade 2 follicular lymphoma
  • 12 months later he complained of continued weight loss, increased itching and worsening fatigue; recurrent infections continued
    • He was started on idelalisib 150 mg PO BID