Addressing Treatment Gaps in Follicular Lymphoma
Dr John P. Leonard highlights ongoing clinical trials and therapies of interest in the follicular lymphoma pipeline and explains how progress in the field will help address ongoing treatment challenges.
John P. Leonard, MD: A number of ongoing trials are directed at trying to better meet the needs of patients with follicular lymphoma. One area is that early progressor group. About 20% of patients present with recurrence within 2 years of initial therapy. That’s a group of patients who have a less favorable overall survival. We are working hard to identify those groups of patients as well as decide if they should be treated differently.
There’s an ongoing SWOG-led study that’s focused on this patient population, looking for biomarkers. They’re trying to sort out if they should be treated with chemoimmunotherapy, a PI3-kinase-based approach, or a lenalidomide-based approach, essentially asking if 1 of these novel approaches should be prioritized in patients with early progression.
In the other group of patients—the majority of patients who are not likely to die from follicular lymphoma but die with follicular lymphoma—quality of life is the key priority. If you can identify a patient and know that they aren’t going to die from the disease, then managing their disease in the long term is an important goal. Trying to tailor treatment to the patient’s optimal quality of life would be an important objective.
Finally, we have a number of new agents that are coming along in follicular lymphoma. We have new PI3 kinase inhibitors, antibody-drug conjugates, bispecific antibodies, CAR [chimeric antigen receptor] T-cell therapies. We have tazemetostat, an EZH2 inhibitor. There are a number of other approaches that clearly have activity in follicular lymphoma. The key challenges are to sort out for when and for whom we should be using these drugs.
That said, the future is bright. We’re going to see lots of progress over the coming years for the treatment of patients with follicular lymphoma.
Transcript edited for clarity.
Case: A 72-Year-Old Woman With Follicular Lymphoma
Initial Presentation
- A 71-year-old woman complains of a 5-month history of occasional fevers, decreased appetite, fatigue, and an unintentional 7-lbs. weight loss
- PMH: unremarkable
- PE: palpable left axillary lymph nodes ~ 4 cm and bilateral cervical lymph nodes ~ 3 cm; spleen palpable 4.5 cm below costal margin
Clinical Work-Up
- Labs: ANC 1.5 x 109/L, WBC 11.8 x 109/L, 42% lymphocytes, Hb 9.6 g/dL, plt 100 x 109/L, LDH 325 U/L, B2M 3.7 µg/mL; HBV negative
- Excisional biopsy of the axillary lymph node on IHC showed CD 20+, CD 3+, CD5+, 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 left axillary, mediastinal, and bilateral para-aortic lymphadenopathy (4.2 cm, 5.3 cm, 3.6 cm, and 3.5 cm respectively)
- Ann Arbor Stage IV; ECOG 0
Treatment
- She was treated with R-CHOP for 6 cycles; continued rituximab maintenance 375 mg/m3; achieved partial response
- 6 months later, she complained of increasing frequency of fevers and chills
- Repeat PET/CT revealed progression of disease
- She was started on bendamustine + obinutuzumab for 6 cycles and continued maintenance on obinutuzumab
- Repeat lymph node biopsy grade 2 follicular lymphoma
- 12 months later, she complained of increased weight loss and fatigue
- She was started on idelalisib 150 mg PO BID and achieved partial response
- She experienced grade 2 diarrhea, which was successfully managed
