Topline Presentation Points
Follicular lymphoma snapshot: outcome after relapse
- Median survival for follicular lymphoma approaches 20 years, but…
- PFS and OS decline with each subsequent relapse
- Early relapse (POD24) predicts 5 yr OS of 50%
FL remains important cause of death
FL: Clinical categories and treatment options
Chemoimmunotherapy in rel/ref FL
- Benda-based regimens yield med PFS 2 years
- Can BR/BO be backbone for more agents?
Immunomodulatory agents
AUGMENT RP3 Len-ritux vs. Placebo-ritux
- Lenalidomide in relapsed (not refractory) FL:
- Results (R2 only):
- Med PFS 39.4m (vs. 14m for R-pbo)
- ORR 78%, CR 34% (Andorsky DOI: 10.1200/JCO.2019.37.15_suppl.7513 Journal of Clinical Oncology 37, no. 15_suppl (May 20, 2019) 7513-7513)
- MAGNIFY
- Phase IIIb interim analysis of induction R2
- OR 73% CR 45%
(Leonard J Clin Oncol 2019 May 10;37(14):1188-1199)
- Will obinutuzumab offer incremental benefit and superiority?
PI3K inhibitors in rel/ref FL
- Three agents FDA-approved – Idelalisib, Copalisib and Duvelisib
- All tested in heavily pretreated, refractory patient population
- Median OS for idela and duvelisib approximately 2 years (more refractory disease)
- Low CR rates
- Toxicity (not discussed) is a limitation for combination therapy for some agents
Salles Haematologica 2017 Apr;102(4):e156-e159; Dreyling Ann Oncol 2017 Sep 1;28(9):2169-2178;
Flinn J Clin Oncol 2019 Apr 10;37(11):912-922
- Umbralisib: new PI3Kd and CK1e inhibitor (FDA approved 2021)
- More selective for PI3Kd
- Inhibits CK1e (Treg modulation)(Burris Lancet Oncol 2018 Apr;19(4):486-496)
(Umbralisib in rel/ref indolent lymphomas)
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- Single arm trial (n=208)
- RR FL, MZL, SLL
- N=117 with FL
- DOSE: 800mg orally daily
- ORR 45% (CR 5%)(Fowler J Clin Oncol 2021 May 20;39(15):1609-1618)
EZH2 Inhibitor
- Tazemetostat monotherapy in rel/ref FL
- demonstrated durable, single-agent, antitumor activity in R/R FL patients with activating mutations (MT) or wild-type (WT) EZH2
- Open label phase II trial:
(Morchhauser ASH 2019)
CAR T
- ZUMA-5 Axi-cel
- March 2021 approved r/r FL with > 2 lines of therapy (Jacobson ASH 2020 Abstract 700)
- ELARA: Tisa-cel in r/r FL
- Promising safety profile
- Comparing cytokine release syndrome and neurotoxicity
- In ELARA trial most CRS (75%) and all neurotoxicity (100%) occurred in patients with bulky disease
Schuster ASCO 2021 Abstract 7508: Efficacy and safety of tisagenlecleucel (Tisa-cel) in adult patients (Pts) with relapsed/refractory follicular lymphoma (r/r FL): Primary analysis of the phase 2 Elara trial
- Which indolent lymphoma patients should be considered for CAR-T?
- Patient identification is key!
- The vast majority of patients with FL do well without aggressive treatments
- Disease characteristics:
- early POD, double refractory, multiple prior regimens with sequentially shorter PFS
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- Patient characteristics:
- No upper age limit, adequate cardiac/renal/pulmonary/neurologic reserve
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- Bulky disease and need for bridging therapy are poor prognostic factors
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- No clear difference between axi-cel and tisa-cel in terms of efficacy in FL
- Marginal zone lymphoma needs more data
Emerging class of agents: bispecific antibodies
- Odronextamab
- Glofitamab
- Mosunetuzumab
- Epcoritamab
