Exploring Options After Second-Line Relapse in FL

Christopher R. Flowers, MD:So there are other alternatives for therapy in the relapsed and refractory setting. Obinutuzumab is 1 of the agents that we might think about in this setting. That’s been best tested in the relapse setting in combination with bendamustine. And since she had bendamustine in her first-line therapy, using obinutuzumab plus bendamustine may not be the best treatment option for this particular patient, given that serial treatments with chemoimmunotherapy, particularly bendamustine, might lead to further cytopenias. And so that’s a possibility but not 1 that I would necessarily select for this particular patient.

So for patients who relapse after 2 regimens of chemoimmunotherapy, there are a number of different treatment options that are now available. The Bruton tyrosine kinase [BTK] inhibitors have been agents that have been well developed and well utilized and approved for use for patients with mantle cell lymphoma [and] approved for use for patients with CLL [chronic lymphocytic leukemia]. But in follicular lymphoma, the responses to ibrutinib are much lower, and it is not approved in this setting for patients with follicular lymphoma.

A BTK inhibitor, while [that is an] orally available [agent], is not necessarily something that I would select for this type of patient or for patients with follicular lymphoma in general who have relapsed after therapy.

Rituximab as a single agent sometimes could be considered as an agent that is approved in the relapsed setting. Again, for someone who has failed chemoimmunotherapy with 2 regimens and had a relatively short relapse, that would be an agent that as a single agent is unlikely to provide much in the way of efficacy.

The other agents that are approved in this space include 3 PI3 kinase inhibitors: idelalisib, duvelisib, copanlisib. As their name implies, those are 3 different forms of PI3 kinase inhibitors that inhibit various forms of the PI3 kinase pathways. So idelalisib is an inhibitor of PI3 kinase delta almost exclusively. Copanlisib is a pan PI3 kinase inhibitor that inhibits forms of alpha, beta, gamma, and delta PI3 kinase. And duvelisib is a dual inhibitor predominantly of gamma and delta PI3 kinase. And those have all been approved in exactly the situation for patients with relapsed and refractory follicular lymphomas.

When you look at idelalisib in particular, the agent this patient received that is a drug that has efficacy across a range of low-grade lymphomas and is approved in follicular lymphoma and in CLL. Its approval in CLL predominantly is in combination with rituximab. For patients with follicular lymphoma, it’s an agent that is used alone and used alone as an oral inhibitor at the [dosage] that she received, 150 mg given twice daily.

Using that regimen, when you look at the waterfall plots for patients who receive that agent, the majority of patients with follicular lymphoma responded in the relapsed and refractory setting. And when you look at the benefits of this agent, the progression-free survival for patients across this trial was about 11 months. And I think importantly, when you look at the progression-free survival for the agent in comparison [with] what their progression-free survival was with their prior line of therapy, patients tended to have longer progression-free survival with idelalisib compared [with] their prior line of therapy, suggesting that this is providing benefits, and particularly benefits over chemoimmunotherapy, in the relapsed and refractory setting. There are other agents that are also approved in this space, and those other PI3 kinase inhibitors also have similar waterfall plots and similar progression-free survival.

Those guidelines list those 3 PI3 kinase inhibitors along with other options for therapy in the relapsed and refractory setting, including lenalidomide plus rituximab, which may be another option for patients in exactly this situation.

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