Bispecific Antibodies Gain Ground in Frontline Follicular Lymphoma Management

Vivek Patel, MD

The follicular lymphoma field is cultivating a growing interest in bispecific antibodies for first-line treatment due to their tolerability, convenience, and efficacy potential, according to Vivek Patel, MD. However, he noted that chemoimmunotherapy regimens remain standard.

In an interview with OncLive®, Patel, an assistant professor at Vanderbilt University Medical Center in Nashville, Tennessee, discussed the role of chemoimmunotherapy in the first-line follicular lymphoma setting. For instance, research has shown that bendamustine plus rituximab (Rituxan; BR) may be more effective and better tolerated than rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) for patients with previously untreated, grade 3A follicular lymphoma, supporting its use in this setting.1 BR, as well as lenalidomide (Revlimid) plus rituximab, are included in the National Comprehensive Cancer Network Guidelines as preferred first-line treatments for patients with follicular lymphoma with high tumor burden.2

Patel also explained the emergence of bispecific antibodies in the first-line setting, noting that compared with traditional chemotherapy, this new class of agents may prolong time to next treatment, improve treatment administration convenience for patients, and be more tolerable.

“It’s a promising avenue, and it’s exciting to see what’s going to happen,” he emphasized in the interview.

OncLive: What does the first-line follicular lymphoma treatment paradigm currently look like?

Patel: Follicular lymphoma is one of those tough [diseases for moving] a new treatment to the frontline setting because the treatments we have right now are effective. For asymptomatic patients who have a new diagnosis of follicular lymphoma, observation is reasonable. That’s one [approach you can take] in the frontline setting. Interestingly, the studies that showed that it’s safe to do observation frontline setting were done in the late 1990s, and ever since then, we’ve known that in some patients with follicular lymphoma, these lymphomas will behave indolently, and [approximately] one-quarter of patients will never need treatment through their lifetime.

For localized, low-volume disease—if patients have a localized lymph node—we can potentially cure patients with local therapy like radiation therapy. Then, for patients who have maybe a bit more advanced disease [with] multiple lymph nodes involved above and below the diaphragm, we have rituximab monotherapy, which can work well to delay the time to next treatment. It doesn’t necessarily make patients live longer, but for some patients who have lymph nodes close to an important structure like the ureter with very low–volume disease, [treatment] like rituximab monotherapy is reasonable.

For patients who have more advanced, symptomatic disease—[like] larger lymph nodes, bulky disease, and lots of B symptoms—the standard of care is chemoimmunotherapy with [a regimen] like BR. Alternatively, we can consider novel agents, like lenalidomide. Lenalidomide plus rituximab [can also be used] in the frontline setting. Both BR and lenalidomide plus rituximab were shown to be noninferior to R-CHOP chemotherapy, which is a bit more toxic to patients.

What upcoming or ongoing studies in the frontline setting are you excited about?

Right now, there are studies investigating frontline bispecific antibodies. Those will read out, and [some] will head into the phase 2 setting. These are interesting because patients receiving BR are receiving bendamustine, an alkylator agent that can mess [up their] lives for a 6-month period. Many bispecific antibodies are in subcutaneous formulations. Mosunetuzumab-axgb [Lunsumio] now has a subcutaneous formulation being tested in the frontline setting. We also have epcoritamab-bysp [Epkinly], which also has a subcutaneous formulation.

[With these agents], a patient can come in to receive a subcutaneous shot, as opposed to receiving intravenous chemotherapy with the risk of neutropenia. Many patients with follicular lymphoma who need treatment are older than the age of 60 years, [and the subcutaneous availability of these agents] is promising. If we’re getting such good time to next treatment with BR, we’re going to push that even longer with these immune therapy–type approaches with bispecific antibodies. Looking at those in the frontline setting, are we going to improve overall toxicity and decrease the risk of secondary malignancies?

What are your main messages regarding patient selection for bispecific antibody treatment?

The cautionary point is: What’s going to be the infection rate for these patients? We don’t have enough data to know what that’s going to look like when we push these [bispecific antibodies] up to the frontline setting. It’s hard to apply all the infection data in the later-line settings to a patient in the frontline setting who might receive a fixed duration of therapy or who may already have a healthier pool of lymphocytes than patients who are in a later-line setting who’ve received multiple prior lines of bendamustine or other chemotherapy, or are older.

It’s exciting to think that maybe for a large percentage of patients, a fixed-duration bispecific antibody treatment can provide durable progression-free survival, [and maybe in the future, we can] just retreat them [with these agents]. We can treat patients in their 80s [with bispecific antibodies]. I have patients who are in their early 90s who I’m giving some of these bispecific antibodies to. They are tolerating [these agents] well. Patient selection is important [for bispecific antibody use], but [there is no] age cutoff, and we can consider retreating patients with this therapy, which has little of the toxicities that chemotherapy does.

References

1. Mondello P, Steiner N, Willenbacher W, et al. Bendamustine plus rituximab versus R-CHOP as first-line treatment for patients with follicular lymphoma grade 3A: evidence from a multicenter, retrospective study. Oncologist. 2018;23(4):454-460. doi:10.1634/theoncologist.2017-0037
2. NCCN. Clinical Practice Guidelines in Oncology. B-cell lymphomas, version 2.2025. February 10, 2025. Accessed May 27, 2025. https://www.nccn.org/professionals/physician_gls/pdf/b-cell.pdf