Novel Therapies for Patients With Follicular Lymphoma

Ajay K. Gopal, MD: We’ve come a long way in the treatment of follicular lymphoma. The prognosis is improved. We understand how to risk stratify based not only on the baseline characteristics, but probably more importantly, on the initial remission duration. We now have agents that are not traditional chemotherapies or chemo-antibody therapies, but we still have work to do. Especially for that 20% of patients who have that early relapse, we really need to improve outcomes for those who have a poor prognosis.

I’m very hopeful regarding some of the agents and classes of drugs that are on the horizon. One class of drugs are the T-cell engagers. These are often called bispecific antibodies that basically bring the lymphoma cell in proximity to the T cell—they’re often CD20 and CD3 bispecific, which is a common construct—and these have shown some early promise in follicular lymphoma. We’re hoping that this would be an off-the-shelf immunotherapy that could be effective for patients, particularly those who have chemo-refractory disease.

Taking it up a notch, something that’s already approved for other B-cell malignancies are CAR T cells, chimeric antigen receptor modified T cells. I’m sure many of you are familiar with these. There are studies that are ongoing or have been completed, and we’re awaiting their results in terms of having this as an option, particularly for the highest-risk and fit patients. Someone has to be relatively fit to make it through this therapy. This would be a relatively small subset of follicular lymphoma patients. Nevertheless, for those who really need another option, there are some who could potentially benefit from this therapy. This is potentially a curative strategy.

There are a number of small molecules such as EZH2 inhibitors. We’re hoping that small subset of patients with EZH2 mutations can benefit from agents such as tazemetostat. Then, there are a number of other novel compounds in the pipeline that we’re looking forward to.

So I’m very hopeful regarding where we’re going with follicular lymphoma. We can say to the majority of patients that their lifespan should not be shortened with this diagnosis, and we can manage this as kind of a nuisance disease. But there are still some patients for which this disease will shorten their lifespan, and I’m hopeful that our new approaches will improve their outcomes.

Transcript edited for clarity.

Case:A 69-Year-Old Woman With Follicular Lymphoma

Initial Presentation

• A 69-year-old woman complains of a 5-month history of fatigue, decreased appetite and a 10-bs. weight loss
• PMH: unremarkable
• PE: right axillary and bilateral cervical lymph nodes palpated ~ 3 cm; spleen palpable 4 cm below costal margin
  
  

Clinical Work-up

• Labs: ANC 1.6 x 109/L, WBC 11.8 x 109/L, 40% lymphocytes, Hb 8.9 g/dL, plt 98 x 109/L, LDH 308 U/L, B2M 3.7 µg/mL; HBV negative
• Excisional biopsy of the lymph node on IHC showed CD 20+, CD 10+, BCL2+; follicular lymphoma grade 2
• Bone marrow biopsy showed paratrabecular lymphoid aggregates, 45% involvement
• Molecular genetics: t(14;18) (q32;q21)
• PET/CT showed enlargement of right axillary lymph nodes (3.1 cm, 3.2 cm), diffusely enlarged nodes in the retroperitoneal and lumbar lymph nodes
• Ann Arbor Stage IV; ECOG 1
  
  

Treatment

• She was treated with R-CHOP for 6 cycles with rituximab maintenance; achieved partial response
• 5 months later she complained of increasing fatigue
  • Repeat PET/CT revealed progression of disease
  • She was started on bendamustine + obinutuzumab for 6 cycles and continued maintenance obinutuzumab
  • Repeat lymph node biopsy remained grade 1-2 follicular lymphoma
• 9 months later she complained of chills and low-grade fever
  • She was started on idelalisib 150 mg PO BID