Follicular lymphoma (FL) is one of the most common indolent B-cell non-Hodgkin lymphomas.

For a long time, patients have primarily relied on chemotherapy combined with anti-CD20 monoclonal antibodies, such as rituximab-based regimens. Although most patients can achieve remission in the initial stage, relapse and drug resistance remain central challenges in the treatment of follicular lymphoma.

With the development of cancer immunotherapy, follicular lymphoma is gradually entering the immunotherapy era.

Among these advances, CD20×CD3 bispecific antibodies (BsAbs, “bispecific antibodies”) have become one of the fastest-growing therapeutic directions in hematologic malignancies.

As a China-based pharmaceutical service platform that continuously follows global innovative drugs and cross-border healthcare information, DengYueMed also regularly compiles updates on emerging immunotherapies in follicular lymphoma (FL) and other hematologic malignancies, helping patients understand evolving treatment options.

Why Does Follicular Lymphoma Tend to Relapse?

Follicular lymphoma is typically slow-growing, and many patients are not in an aggressive disease state at diagnosis. However, this indolent nature does not mean it is curable.

Its key characteristics include:

● Frequent relapse after treatment

● Gradual development of drug resistance in some patients

● Shortening remission duration after multiple lines of therapy

● A small proportion of cases may transform into aggressive lymphoma

Although traditional therapies can control the disease, they rarely eliminate residual tumor cells completely. In particular, in second-line and later treatment settings, patients often face limited therapeutic options.

This is why immunotherapy has become a major research focus in recent years.

Why Are Bispecific Antibodies Gaining Attention?

The core mechanism of bispecific antibodies is the simultaneous binding of two different targets.

Taking the most widely studied CD20×CD3 bispecific antibody in follicular lymphoma as an example:

● One arm binds CD20 on B cells

● The other arm binds CD3 on T cells

This structure brings T cells into close proximity with tumor cells, thereby directly activating immune-mediated tumor killing.

In simple terms, bispecific antibodies act as a “bridge” between the patient’s immune system and the tumor.

Compared with conventional chemotherapy, their advantages are becoming increasingly evident:

1. More precise immune-mediated killing

They primarily target malignant CD20-positive B cells, reducing damage to normal tissues.

2. Independent of pre-existing anti-tumor immunity

Even in an immunosuppressive tumor microenvironment, bispecific antibodies can actively recruit T cells for tumor attack.

3. Activity in relapsed/refractory patients

Many patients who have failed multiple prior therapies may still respond to bispecific antibodies.

4. Potential to reduce reliance on chemotherapy

In the future, some patients may gradually move toward a “chemotherapy-sparing” treatment era.

CD20×CD3 Bispecific Antibodies Are Transforming the FL Treatment Landscape

Currently, four CD20×CD3 bispecific antibodies have been approved globally:

●      Mosunetuzumab

●      Glofitamab

●      Epcoritamab

● Odronextamab

Among them, odronextamab is still in clinical development in China, while the other products have already been approved in China.

Notably, Epcoritamab was approved in China on May 15, 2026, providing a new CD20×CD3 bispecific antibody treatment option for patients with relapsed or refractory follicular lymphoma.

For more information about Epcoritamab, readers can refer to the article: Epcoritamab Approved in China for Follicular Lymphoma, Bringing a New CD20×CD3 Bispecific Therapy Option.

Multiple studies have shown that bispecific antibodies can achieve high response rates in relapsed or refractory follicular lymphoma, with some patients reaching complete remission (CR).

This advancement is particularly meaningful for patients who have undergone multiple prior lines of therapy.

Subcutaneous Administration Is Improving Treatment Convenience

In addition to efficacy, the route of administration is also evolving.

Earlier bispecific antibodies often required intravenous infusion with relatively long administration times. New-generation agents are increasingly using subcutaneous injection, offering several advantages:

● Shorter administration time

● Reduced healthcare resource utilization

● Improved patient adherence

● Potentially better management of certain adverse events

In this context, Epcoritamab has attracted significant attention.

Will Bispecific Antibodies Replace CAR-T Therapy?

This is a common question among patients.

In reality, bispecific antibodies and CAR-T therapy are better understood as complementary rather than competitive approaches.

Characteristics of CAR-T therapy:

● Personalized cell therapy

● Potential for deep and durable remission in some patients

● Long manufacturing time

● High treatment cost

● Requires specialized treatment centers

Characteristics of bispecific antibodies:

● “Off-the-shelf” therapy

● No need for cell manufacturing wait time

● Faster treatment initiation

● Flexible administration

● Easier to scale and access

In future clinical practice, bispecific antibodies may be used:

● As a bridge to CAR-T therapy

● In patients who relapse after CAR-T

● In patients not eligible for CAR-T

● Earlier in the treatment line

Therefore, bispecific antibodies are likely to become an important component of the follicular lymphoma immunotherapy landscape.

Follicular Lymphoma Treatment Is Entering the Era of Immunotherapy Combinations

In the future, FL treatment may no longer rely on a single modality but instead evolve into a multi-immunotherapy combination era.

Current research directions include:

● Bispecific antibodies combined with anti-CD20 monoclonal antibodies

● Bispecific antibodies combined with immunomodulatory agents

● Bispecific antibodies combined with CAR-T therapy

● Earlier-line use of bispecific antibodies

● Maintenance strategies using bispecific antibodies

With more clinical data emerging, treatment goals in follicular lymphoma are gradually shifting from simply extending remission toward long-term disease control and even functional cure.

Conclusion

From the chemotherapy era to the targeted therapy era, and now to the rapidly evolving immunotherapy era, the treatment landscape of follicular lymphoma is being fundamentally reshaped.

The rise of CD20×CD3 bispecific antibodies not only changes the treatment pathway for relapsed or refractory patients but also brings new possibilities for long-term disease control.

With next-generation agents such as Epcoritamab gradually being approved and adopted, follicular lymphoma treatment is accelerating toward a more precise, less chemotherapy-dependent, and increasingly personalized immunotherapy era.

The China pharmaceutical distributor DengYueMed will continue to compile developments in bispecific antibodies, CAR-T therapies, and other emerging immunotherapies, continuously updating treatment options and cutting-edge medical information.