Bispecific Antibodies, Novel Combinations Highlight Continued Treatment Evolution in Follicular Lymphoma

In an interview with OncLive^®, David C. Fisher, MD, spotlighted recent data to emerge in the follicular lymphoma space, including findings for the EZH2 inhibitor tazemetostat (Tazverik) used in combination therapy and data for the bispecific antibody epcoritamab-bysp (Epkinly).

Fisher, who is an assistant professor of medicine at Harvard Medical School and a physician at Dana-Farber Cancer Institute in Boston, Massachusetts, also elaborated on the clinical significance of the growing treatment options for follicular lymphoma.

In a previous article, Fisher broke down data for BTK inhibitors in the treatment of chronic lymphocytic leukemia.

OncLive: What data have been seen thus far for tazemetostat in combination with rituximab (Rituxan) and lenalidomide (Revlimid) in patients with relapsed/refractory follicular lymphoma?

Fisher: At the 2023 ASH Annual Meeting, [data were presented from the phase 1b SYMPHONY-1 trial (NCT04224493)] looking at tazemetostat in combination with rituximab and lenalidomide.1 We know that rituximab plus lenalidomide has activity in follicular lymphoma, and so does tazemetostat [as monotherapy]. This trial was looking at the combination regimen, [and data were presented] with 22.5 months of follow-up.

Tazemetostat is an EZH2 inhibitor, and it's approved [by the FDA] for patients with [EZH2-positive] follicular lymphoma who have relapsed/refractory disease and have received 2 or more prior therapies.

[SYMPHONY-1] looked at different dosings of tazemetostat with standard rituximab plus lenalidomide. After 12 months of combination therapy, tazemetostat was used as a maintenance therapy until disease progression, adverse effects, or withdrawal.

[Data showed] 54.8% of patients had a complete response [CR], and 40.5% of patients had a partial response; 4.8% had stable disease. The overall response rate [ORR] was 90.9%. and [responses] were seen in patients who were EZH2 wild-type and those harboring EZH2 mutations. [The ORRs in these populations] were 88.9% and 100%, respectively. [The] 18-month progression-free survival [PFS] rate was 79.5%; the 18-month duration of response [DOR] rate was 81.0%. [Notably, PFS and DOR rates were higher] in the 800-mg group.

What studies have explored the use of bispecific antibodies in relapsed/refractory follicular lymphoma?

An exciting set of drugs in follicular lymphoma are the bispecific antibodies. The [phase 1/2] EPCORE1 NHL-1 trial [NCT03625037] assessed epcoritamab in patients with relapsed/refractory follicular lymphoma.²

In the study, [the majority of] patients had advanced-stage disease, and most had Follicular Lymphoma International Prognostic Index high-risk disease. Patients had multiple lines of [prior] therapy with a median of 3. Nearly half the patients had progression of disease within 24 months of starting prior therapy. Over half [of enrolled] patients had primary refractory disease, and 69% had disease refractory to prior therapy. The ORR was 82% with a CR rate of 63%, and the medium PFS was 15.4 months. The median overall survival was not yet reached.

What is the clinical significance of the findings from the phase 2 EPCORE NHL-6 trial (NCT05451810) evaluating epcoritamab given in the outpatient setting?

[Epcoritamab] is [typically] given on days 1 and 8 as outpatient [therapy] with dose escalation from 0.16 mg to 0.8 mg, then the [first] full dose of 48 mg at day 15 is usually given in the inpatient setting in order to watch for cytokine release syndrome [CRS].

In [EPCORE NHL6], an extra [step-up dose] was added at day 15, and the first full 48-mg dose was pushed back to day 22. With dose escalation, patients seemed to have better control of CRS, suggesting that this can now be given entirely as an outpatient [therapy]. That would be a huge step for many groups and centers to be able to use this drug [entirely in the outpatient setting].

What advice would you give to clinicians seeking to integrate these newer treatment options for patients with follicular lymphoma?

Many centers and groups have to get used to using these drugs, as well as evaluating and treating for [things such as] CRS. It's unusual that we need to use IL-6 inhibitors like tocilizumab [Actemra] with bispecific antibodies as we do with CAR T-cell therapy. Therefore, bispecific antibodies could be more easily adapted by many groups compared with CAR T-cell therapy.

Epcoritamab is [delivered] subcutaneously, which some groups find easier. Glofitamab-gxbm [Columvi] is approved for 9 months of therapy, [whereas] epcoritamab is approved for indefinite therapy. In practice, it's hard to use indefinite therapy, so we should think of both as being time-limited therapy. It's just a matter of getting a little more used to these drugs. If we can do step-up dosing and keep patients out of the hospital, that'll make things a lot easier.

References

1. Salles G, Park SI, Phillips TJ, et al. Tazemetostat in combination with lenalidomide and rituximab in patients with relapsed/refractory follicular lymphoma: updated phase 1b results of Symphony-1 with 22.5 months follow-up. Blood. 2023;142(suppl 1):3035. doi:10.1182/blood-2023-179910
2. Linton K,Jurczak W, Lugtenburg P, et al. Epcoritamab SC monotherapy leads to deep and durable responses in patients with relapsed or refractory follicular lymphoma: first data disclosure from the Epcore NHL-1 follicular lymphoma dose-expansion cohort. Blood. 2023;142(suppl 1):1655. doi:10.1182/blood-2023-179887