Future Directions for Treatment of Relapsed/Refractory Follicular Lymphoma
Kami Maddocks, MD, lists the future directions and unmet needs present in treating relapsed/refractory follicular lymphoma.
Kami Maddocks, MD: When we look at the future of follicular lymphoma [FL] and some of the unmet needs, I think 1 of the first things is identifying if we can better decide therapy for patients at initial presentation. As I mentioned, there are prognostic scores, but we don‘t know how to use that to decide treatment. Deciding response and things like maintenance therapies, so minimal residual disease, might be something in the future that we can use to help us to decide if maintenance is appropriate for those patients at high-risk for relapse. Those patients as I mentioned who are at high-risk for death from their FL or have lower overall survival are those patients who relapse within the first 2 years of treatment, and we don‘t know the best treatment for those patients. Although we think maybe using different types of therapy with different mechanism of action in the second-line setting might be more ideal than using chemoimmunotherapy, we don‘t know that and there‘s a large cooperative group trial now trying to see if we can define the best treatment for these high-risk patients.
Chimeric antigen receptor [CAR] T-cell therapy is newly approved for patients with FL after progression after 2 or more prior therapies, but this is also associated with significant toxicities, such as cytokine release and neurotoxicity. I think further defining the right patient population for these, as patients who have gotten very long remissions to their initial 2 therapies probably aren‘t necessarily the most ideal candidates to use this in that setting, but those patients who have done poorly with the initial therapy from the standpoint of not getting into remission or having short time before progression are probably ideal candidates for these therapies. Some of the more promising therapies under development include bispecific therapies, so it‘s targeted CD20 by CD3, these have shown to have good early responses in the B-cell malignancies, including FL, but not the same risk of toxicity with the CRS [cardiorenal syndrome] as the CAR T cells. Other antibody-drug conjugates including those targeting CD [cluster of differentiation]19, and then CD19 antibody therapy is also under investigation for FL.
Transcript edited for clarity.
Case: A 74-Year-Old Man With Relapsed/Refractory Follicular Lymphoma
Initial presentation
- A 74-year-old man complains of a 6-month history of fatigue, occasional fevers, decreased appetite, fatigue, and an 8-lb weight loss
- PMH: unremarkable
- PE: palpable right axillary and cervical lymph nodes, palpable ~ 3 cm in both locations; spleen palpable 4.5 cm below left costal margin
Clinical Workup
- Labs: ANC 1.6 x 109/L, WBC 11.2 x 109/L, 44% lymphocytes, Hb 9.6 g/dL, plt 98 x 109/L, LDH 315 U/L, B2M 3.5 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, 4% involvement
- Molecular genetics: t(14;18) (q32;q21)
- PET/CT showed enlargement of right axillary, cervical, and mediastinal lymphadenopathy (3.3 cm, 3.1, cm and 4.6 cm respectively)
- Ann Arbor Stage IV; ECOG 0
Treatment
- He was treated with R-CHOP for 6 cycles, achieved complete response and continued rituximab maintenance
- 24 months later he complained of increasing weight loss, fever and drenching sweats as well as more enduring fatigue and new onset itching; he was currently taking antibiotics for his 3rd bacterial infection in the past year
- Repeat PET/CT revealed progression of disease
- He was started on bendamustine + rituximab for 6 cycles and continued on rituximab maintenance
- Repeat lymph node biopsy grade 2 follicular lymphoma
- 12 months later he complained of continued weight loss, increased itching and worsening fatigue; recurrent infections continued
- He was started on idelalisib 150 mg PO BID
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