Approaching a Case of High-Risk Follicular Lymphoma

Peter Martin, MD:This is a case of a 72-year-old man who has a past medical history of some gastroesophageal reflux and obstructive sleep apnea, who presented to his physician with a several-months-long history of progressive fatigue and a 15-pound weight loss over the past 6 months. He, as well, had noticed a right supraclavicular air mass, and that was what ultimately led him to come to his physician. His physician noticed on the physical exam that there was a supraclavicular mass and did some lab testing, which revealed a slightly elevated LDH, a hemoglobin of 9.9, platelets of about 110, a slightly low total white blood cell count with a normal neutrophil count. He subsequently sent him for imaging, which revealed diffuse lymphadenopathy. He, from there, was referred to a surgeon who did a biopsy of one of the lymph nodes, which revealed grade 2 follicular lymphoma, and was referred from there to a hematologist who saw the cytopenias and did a bone marrow biopsy, which also found involvement of follicular lymphoma in the bone marrow.

At that point, the patient underwent a PET/CT scan, which showed, again, diffuse lymphadenopathy. The maximum size of the lymph nodes was about 5 cm to 6 cm—so, relatively large. And the maximum SUV was in the 8 to 9 range. So, nothing particularly concerning for a histological transformation to diffuse large B-cell lymphoma. His FLIPI score, on the basis of this information, is actually 5. His age is more than 60, he has an elevated LDH, his stage is 4, his hemoglobin is low, and he has more than 3 lymph node sites involved. So, unfortunately, it doesn’t really get much higher risk than that in terms of a FLIPI score. On that basis, his hematologist initiated therapy with R-CHOP. He achieved a partial response and was subsequently treated with rituximab maintenance for 2 years.

One of the first considerations when we see somebody with newly diagnosed indolent follicular lymphoma is, does this patient need treatment? My bias is to consider observation in people who are asymptomatic and have relatively low tumor burden follicular lymphoma. In this case, however, the patient does not have low tumor burden follicular lymphoma, he has diffuse lymphadenopathy, fairly large sizes in the 5 cm to 6 cm range. He has cytopenias, and, most importantly, he has symptoms. He has fatigue and weight loss. So, he clearly needs some sort of treatment.

Then we start to consider, what are the best options regarding therapy? And when we think of both those treatment options, we have to, of course, consider their goals of therapy. Are we going to cure this patient with follicular lymphoma? That’s not a typical goal. So, our goal is to prolong life and do it in a way that minimizes symptoms related to lymphoma and symptoms related to treatment.

One of the interesting considerations with respect to that concept of prolonging life is that people with follicular lymphoma now are living longer than they ever have in the past. When we look at the survival—based on actuarial tables of somebody with average age of diagnosis of follicular lymphoma, so say age 70—on average, a person who’s 70 years old will live about 14 to 15 years if they’re otherwise healthy. Interestingly, somebody with follicular lymphoma is also expected to live about 14 or 15 years. And data from Europe and the Mayo Clinic and others have suggested that although the majority of people with follicular lymphoma may die from causes related to lymphoma or treatment of lymphoma, they don’t seem to have a survival that’s any different than a population of people without lymphoma.

So, in other words, most people with follicular lymphoma don’t experience excess mortality due to the lymphoma, they just experience excess morbidity. They feel the lymphoma, they feel the treatments for lymphoma. So, as long as we’re including rituximab somewhere in the treatment, which we know improves survival, our goals really are not so much focused on making this person live forever. Our goals really have to be around how can we help this person to have the best life that they could possibly have with lymphoma.

Transcript edited for clarity.

October 2014

• A 72-year-old man presents to his physician complaining of fatigue lasting several months, recent weight loss of 15 lbs. and a mass on his right side of neck
• PMH: GI reflux controlled on PPI, obstructive sleep apnea
• PE: Right supraclavicular lymph node (7 cm.), spleen palpable 5 cm. below the costal margin
• Performance status, 1
• Laboratory findings:
  • Hb, 9.9 g/dL ,
  • Leukocytes, 3.21 X 10⁹/L
  • Platelets, 110 X 10⁹/L
  • AST, 162 U/L; ALT 201 U/L
  • LDH, 302 U/L
• Excisional biopsy of the right supraclavicular node:
  • IHC staining, CD10+, Bcl2+, CD5-
  • Follicular lymphoma, grade 2
• Bone marrow; paratrabecullar infiltration by small cleaved lymphocytes
• PET-CT showed enlargement of right supraclavicular lymph node (3 X 7 cm) and 3 mediastinal lymph nodes (3.2 cm, 3.5 cm, 4.4 cm); diffusely enlarged nodes in the retroperitoneal, mesentery, and inguinal regions: SUVmax, 9
• FLIPI, 5 points, high risk
• The patient was treated by the local oncologist with R-CHOP (6 cycles)
• Post-treatment he achieved a partial metabolic response
• He was continued on rituximab maintenance therapy and his disease remained stable

July 2016

• 23 months later, the patient complained of his symptoms returning
• PET revealed enlargement of the affected mediastinal nodes
• SUVmax of all nodes was 12
• Repeat CT revealed progression of disease
• The patient was started on bendamustine + rituximab (6 cycles) and achieved a partial response after completing induction therapy

January 2018

• Sixteen months later, the patient reports feeling tired but could resume most normal activities (ECOG 1)
• PET with diagnostic CT showed diffuse¹⁸F-FDG uptake in multiple lymph nodes and spleen; the largest involved nodes are the right supraclavicular (6.2 cm), left mesenteric (4.8 cm), and splenic hilar (2.7 cm) nodes
• Repeat biopsy showed grade 2 follicular lymphoma
• The patient was started on copanlisib
• After three months, he developed a partial response with>50% reduction in lymphadenopathy in all involved nodes