Emerging Options and the Future of Follicular Lymphoma

John Pagel, MD:The good news is that there are tons of new exciting therapies in development for follicular lymphoma. We do know that, at this point, we don’t cure these patients with standard treatments, but we can help people live for long periods of time. In fact, most patients will live full lives and do very well, but they will continue to relapse and we continue to need to develop novel therapies for these patients. Bispecific antibodies are a very exciting novel approach in development. Certainly we recognize that CAR [chimeric antigen receptor] T-cell therapies have been a major advance for more aggressive lymphomas, and we’ll see if we can get it to work really well as well in patients with follicular lymphoma.

There’s a drug that’s not approved in follicular lymphoma—but it’s something always to consider and we need to see more data on it—but that’s venetoclax, a BCL2 inhibitor. Definitely has activity in follicular lymphoma. We’ll see where it goes in follicular lymphoma, but it’s something to keep in your back pocket and remember that it can have activity here.

There are a variety of new PI3 kinase inhibitors in development as well. We’ve been talking about the first-generation inhibitors, but there are new ones in development that are very efficacious, and we’re figuring out ways to use them with less toxicity, or we’re developing ones that actually appear to be better tolerated, and hopefully that’ll be a major advance for us in the future.

And there’s all kinds of new, exciting targets that are targeted therapies, oral agents in development. Others that target different spots in the B-cell signaling cascade, just like targeting PI3 kinase. You could image that that’s going to be a [particularly] important advancement as well for developing drugs that target new, different proteins inside the malignant lymphoma cell.

And lastly, as we’ve talked about and what I want to reiterate, I think Revlimid is going [to continue to be a game changer] in patients with follicular lymphoma. The R-squared [Revlimid and rituximab] regimen is something we should continue to remember as an important option.

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