Relapse After Second-Line Therapy in Follicular Lymphoma - Episode 5

Managing Follicular Lymphoma as a Marathon, Not a Sprint

Christopher R. Flowers, MD:When we think about the relapsed and refractory follicular lymphoma, that is a disease entity that I think of as something that you need to manage as a marathon, not a sprint. And there are a number of different treatment options there. Idelalisib and the other PI3 kinase inhibitors sit in the armamentarium of a number of agents that look to be active in that space. And I think across the course of therapy for patients, it’s something that we could use for patients who become relapsed and refractory, particularly when chemoimmunotherapy is no longer working.

Follicular lymphoma is a disease, as I mentioned, that really needs to be managed as a marathon, not a sprint. And so when I talk to patients about the management of their disease, I talk to them not just about what kind of treatment are we going to give right now, but what kind of treatment do we need to have available next, and what do we use next, and what do we use next after that? And thinking about that within the continuum, there really are some gaps that we currently have in therapy.

This particular patient highlighted 1 of those, and that’s patients [who] relapse early after therapy. And that is a particular patient population where there’s a strong unmet need. Particularly those patients who relapse after first-line therapy, a subsegment of those patients or patients for whom autologous stem cell transplantation might be an option and may be an option that can produce prolonged disease-free survival. But the majority of patients with follicular lymphoma tend to be older, [because] they’re diagnosed in their late 60s and 70s, and stem cell transplant typically is not an option. For an even smaller population of patients, allogeneic stem cell transplantation is still an option but really provides benefits for relatively few patients.

So there are clearly unmet needs both in terms of the use of novel therapies, ideally in novel oral therapies, that can be used for these patients. As I mentioned, novel PI3 kinase inhibitors are being looked at in this space. Bruton tyrosine kinase inhibitors are being looked at in combination therapies that might have a role for these particular patients. Lenalidomide and other IMiDs [immunomodulatory drugs] are being looked at for patients. Like many other cancers, the checkpoint inhibitors are being looked at in follicular lymphoma that have had limited opportunities, at least in that space so far. But there are maybe more opportunities there in the future.

Follicular lymphoma is a kind of disease that we know—among patients who have been observed at diagnosis—that about 2.6% of patients actually have spontaneous reduction and resolution of their disease. And so it’s a disease that the immune system itself can help to regulate. And so there may be a number of opportunities in the future for being able to modify the immune system by revving up the immune system to be able to attack follicular lymphoma. And I think that’s a huge opportunity in the future.

Like other lymphomas, CAR [chimeric antigen receptor] T-cell therapies have been explored as 1 particular way of utilizing the immune system, and I think those hold an additional promise for a patient with follicular lymphoma.

Transcript edited for clarity.

Case:A 72-Year-Old Woman With Relapsed Follicular Lymphoma

H & P:

  • A 75-year-old woman presented with severe fatigue and weight loss
  • Was diagnosed with inguinal contiguous stage II follicular lymphoma (FL) 4.5 years ago; completed BR and achieved PR that persisted for almost 4 years
  • Started treatment with R-CHOP for extensive mediastinal FL 6 months ago; had achieved PR by 3 months before symptoms returned
  • PMH: Type 2 diabetes X 10 years, controlled on basal insulin and SGLT2 inhibitor
  • PE: Swelling present in right axillary lymph nodes; not tender to touch; no crackles or rales in lungs; no history of pneumonia; has received flu and PPV23 vaccination
  • ECOG performance status: 1
  • Biopsy showed grade 2 FL without transformation
  • Labs:
    • eGFR = 72 mL/min/1.732
    • AST/ALT: within normal range
    • ANL: 1350 /mm3
    • Platelets: 100,00 /µL
    • Hemoglobin: 10 g/dL
    • LDH: 275 U/L
  • Imaging: PET/CT revealed axillary lymphadenopathy, with largest mass 7.2 cm
  • She was started on idelalisib 150 mg b.i.d.
  • After 10 days, she called with concerns about diarrhea, which she has been experiencing on average 4 times daily for the past few days