Dr Patel on Ongoing Research With Subcutaneous Bispecific Antibodies in Frontline Follicular Lymphoma

“These [studies are] really interesting, because [for] patients getting bendamustine and rituximab as their treatment, they’re getting an alkylator agent, which can mess somebody’s life up for a 6-month time period. Many of these are subcutaneous formulations; mosunetuzumab now has a subcutaneous formulation being tested in the frontline setting.”

Vivek G. Patel, MD, an assistant professor of medicine in the Division of Hematology Oncology at Vanderbilt University Medical Center, discussed notable upcoming and ongoing studies for patients with follicular lymphoma in the frontline setting.

The frontline investigation of bispecific antibodies in patients with follicular lymphoma is ongoing, and many investigations are expected to transition into phase 2 settings, Patel noted. These agents are of particular interest because current frontline regimens, such as bendamustine plus rituximab (Rituxan; BR) expose patients to cytotoxic chemotherapy, including alkylating agents that can significantly affect quality of life over a 6-month course, he explained. In contrast, many bispecific antibodies are being developed in subcutaneous formulations, including mosunetuzumab-axgb (Lunsumio) and epcoritamab-bysp (Epkinly), which are under evaluation for use in the frontline setting, Patel said.

From a patient experience standpoint, the prospect of receiving subcutaneous immunotherapy rather than intravenous chemotherapy—which has associated risks, such as neutropenia—is especially appealing, particularly for the follicular lymphoma population, which often includes patients older than 60 years of age, Patel remarked. Given the durable time to next treatment seen with BR in patients with this disease, investigators are optimistic that bispecific antibody–based treatment approaches may further extend those outcomes, Patel added.

In addition to potential improvements in efficacy, these regimens may reduce overall toxicity and lower the long-term risk of secondary malignancies, according to Patel. However, infection risk remains a key consideration, particularly in the frontline setting where data are currently limited, Patel cautioned. Infection rates observed in relapsed/refractory populations—often heavily pretreated with prior bendamustine or other cytotoxic regimens—may not accurately predict outcomes in treatment-naive patients, Patel observed.

Ultimately, the potential for fixed-duration bispecific antibody therapy to deliver durable outcomes in a broad patient population—including those in their 80s and 90s—is promising, Patel reported. With careful patient selection, many older adults are tolerating these agents well, and such therapies may offer a retreatment strategy with fewer toxicities compared with conventional chemotherapy, he concluded.