Vivek G Patel, MD, is an assistant professor of medicine in the Division of Hematology Oncology at Vanderbilt University Medical Center.

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.

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Vivek G. Patel, MD, discusses the potential advantages of subcutaneous bispecific antibodies that are being evaluated in frontline follicular lymphoma.
 

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

Dr Patel on the Safety Profile of Bispecific Antibodies in Follicular Lymphoma

“A [primary] takeaway [regarding] current and emerging treatments in follicular lymphoma is the efficacy, but more importantly the safety, of bispecific antibody therapies. When I [examined] the data of bispecific antibody combination and monotherapy treatments, there were very low rates of high-grade cytokine release syndrome or immune effector cell–associated neurotoxicity syndrome.”

Vivek G. Patel, MD, assistant professor of medicine, Division of Hematology Oncology, Vanderbilt University Medical Center, discussed the safety profile of bispecific antibodies for the treatment of patients with follicular lymphoma, which he highlighted during a presentation at a State of the Science Summit™ on hematologic malignancies.

In general, bispecific antibodies, such as mosunetuzumab-axgb (Lunsumio) and epcoritimab-bysp (Epkinly), have shown low rates of high-grade cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS) in patients with follicular lymphoma, both as monotherapy and combination components, Patel began.

Data from the phase 2 Mithic-FL1 trial presented during the 

revealed that patients with follicular lymphoma who received frontline mosunetuzumab (n = 78) experienced any-grade CRS at a rate of 54%; these events were mostly grade 1 (51%) and there were no instances of grade 3 or higher CRS. Notably, there were no reports of ICANS-like toxicities. Findings from the phase 1b/2 EPCORE NHL-2 study (NCT04663347) showed that among 111 patients with relapsed/refractory follicular lymphoma who received epcoritamab in combination with rituximab (Rituxan) and lenalidomide (Revlimid), the incidence of CRS was mostly grade 1 to 2 (50%), with 1% of patients experiencing grade 3 and 4 CRS and no grade 5 events. There was only 1 instance of ICANS, which was low grade and was quickly resolved.

Patel noted that protocols are now in place to optimize step-up dosing with bispecific antibodies and the time to onset of CRS is predictable. Importantly, most instances of CRS can be treated in the outpatient setting, he added. Overall, bispecific antibodies are safe and do not have similar non-relapse mortality rates compared with CAR T-cell therapies, Patel explained.

Bispecific antibodies are safe, effective, and ideal for use in the community-based setting, Patel noted. These agents will enable investigators to further expand access to care for patients with follicular lymphoma, he concluded.

Vivek G. Patel, MD, discusses the safety profile of bispecific antibodies for the treatment of patients with follicular lymphoma.

Dr Patel on Choosing Between Mosunetuzumab and Epcoritamab in Follicular Lymphoma

"Both [mosunetuzumab and epcoritamab] are overall well tolerated in terms of efficacy, though, is there really a difference [between these agents]? We just don't have enough information to answer that.”

Vivek G Patel, MD, an assistant professor of medicine in the Division of Hematology Oncology at Vanderbilt University Medical Center, discussed the clinical similarities and differences between mosunetuzumab-axgb (Lunsumio) and epcoritamab-bysp (Epkinly) for the treatment of patients with follicular lymphoma.

When selecting the appropriate bispecific antibody for patients with follicular lymphoma, is important to discern whether there are meaningful differences between available products, Patel stated. In follicular lymphoma, 2 bispecific antibodies—mosunetuzumab and epcoritamab—have demonstrated efficacy and are FDA approved in the third-line or later setting, Patel stated. Although both agents operate via similar mechanisms—engaging T cells to target and kill B cells—the structural designs differ between these antibodies, Patel stated. Despite the similar functions between these agents, the molecular configurations, or motifs, of these bispecific antibodies are not identical, Patel stated.

When comparing mosunetuzumab with epcoritamab, there are currently insufficient data to clearly define the effects of these structural differences on clinical outcomes, Patel stated. Notably, in large B-cell lymphoma, mosunetuzumab did not demonstrate the same level of efficacy as epcoritamab, which has limited the utility of mosunetuzumab in that population, Patel stated. However, mosunetuzumab appears to align particularly well with the biology of follicular lymphoma, offering substantial efficacy and a favorable adverse effect profile, Patel stated.

In terms of tolerability, the 2 agents have similar safety profiles, and are both associated with low rates of high-grade cytokine release syndrome and rare occurrences of immune effector cell–associated neurotoxicity syndrome, particularly that of higher grade, Patel stated. Overall, both agents are generally well tolerated, Patel stated. Regarding comparative efficacy between the 2, data remain inconclusive, and no definitive determination can yet be made, Patel concluded.

Vivek G Patel, MD, discusses the comparative efficacy and safety profiles of mosunetuzumab and epcoritamab in follicular lymphoma.
 

Vivek G Patel, MD

Articles

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

Dr Patel on the Safety Profile of Bispecific Antibodies in Follicular Lymphoma

Dr Patel on Choosing Between Mosunetuzumab and Epcoritamab in Follicular Lymphoma