Golcadomide (GOLCA) for Relapsed Follicular Lymphoma: A Novel Oral Therapy

Follicular lymphoma (FL) is one of the most common types of indolent non-Hodgkin lymphoma. While it is considered slow-growing, it remains a chronic, relapsing blood cancer.

Many patients respond well to first-line therapy and experience long remissions. However, follicular lymphoma is still not considered curable. Over time, the disease almost always returns — and with each relapse, responses may become shorter and more resistant to treatment.

That is why the development of novel, chemotherapy-free therapies for relapsed follicular lymphoma remains a major priority in hematology.

If you would like a broader overview of available treatment options and active clinical trials, visit our dedicated
👉 Follicular Lymphoma Clinical Trials page

But first, let’s walk through:

• Why new treatments are still needed in follicular lymphoma

• What Golcadomide is, and how it works

• Why the GOLSEEK-4 trial is generating attention

  
  

Why New Treatments Are Still Needed in Follicular Lymphoma

Current treatment options for relapsed follicular lymphoma include:

• Chemotherapy combined with antibodies like rituximab

• Rituximab plus lenalidomide

• New immune-based treatments such as CAR T-cell therapy or bispecific antibodies

• 
  

While these treatments help many patients, they also come with significant challenges:

• Some stop working over time

• Some cause long-term fatigue, infections, or nerve problems

• Some require hospital stays or complex care

  
  

For some patients, treatment itself can feel almost as difficult as the disease.

👉 Many patients still need effective, chemotherapy-free treatments that are easier on the body and easier to live with.

________________________________________

What Is Golcadomide & How it Works?

Golcadomide is an oral (pill) medication designed to treat lymphoma.

It belongs to a newer group of medicines that work through a protein called cereblon—a natural “recycling controller” inside cells. Cereblon acts like a quality control manager, tagging damaged or unwanted proteins for destruction.

Golcadomide is what scientists call a CELMoD agent (cereblon E3 ligase modulator). Essentially, it hijacks this natural cleanup system and reprograms it to specifically destroy cancer-related proteins.

In simple terms, golcadomide acts like a molecular “hitman”—targeting cancer cells in a smarter, more precise way.

Golcadomide is designed to:

• Work especially well in lymph nodes, where follicular lymphoma lives

• Help the immune system fight cancer more effectively

• Directly weaken lymphoma cells themselves

  
  

Golcadomide works in two main ways, both involving specific proteins inside lymphoma and immune cells.

1️- Direct Cancer Cell Killing: Weakening Lymphoma Cells From the Inside

Lymphoma cells depend on certain proteins to stay alive and keep dividing.

Two of the most important are:

• Ikaros (IKZF1)

• Aiolos (IKZF3)

These proteins act like master switches that tell lymphoma cells: how to survive, How to grow, How to hide from the immune system

Golcadomide binds to cereblon, the protein responsible for labeling unwanted proteins for removal. Once bound, golcadomide forces cereblon into an active “closed” shape, like flipping a switch to “ON”.

In this activated state, cereblon specifically targets Ikaros and Aiolos, leading to➡️ Rapid breakdown and removal of these proteins

Without Ikaros and Aiolos, lymphoma cells:

• Lose critical survival signals

• Stop growing

• Become more likely to die

2️- Immune System Activation: Helping the Immune System Fight Back

Follicular lymphoma doesn’t just grow—it actively suppresses the immune system around it.

By removing Ikaros and Aiolos, golcadomide effectively removes the “brakes” on the immune system, allowing the body’s natural defenses to recognize and attack cancer cells.

As a result, golcadomide:

• Increases immune signaling molecules like interleukin-2 (IL-2)

• Activates T cells (the immune system’s attack cells)

• Improves natural killer (NK) cell function

This makes immune cells more alert, more active, and better able to recognize and destroy lymphoma cells.

Golcadomide also strengthens the effect of rituximab, an antibody targeting the CD20 protein on lymphoma cells, by improving immune-mediated killing.

Why Golcadomide Is Different From Older Treatments?

Some patients have already been treated with lenalidomide, which works through a similar pathway.

Golcadomide is different because it:

• Binds cereblon more tightly

• Causes deeper and faster removal of Ikaros and Aiolos

• Can still work even when lenalidomide has stopped working

This is why golcadomide is being studied specifically in relapsed or refractory follicular lymphoma.

________________________________________

Spotlight on the GOLSEEK-4 Clinical Trial

👉 https://app.cancerbot.org/t/NCT06911502

GOLSEEK-4 is a global Phase 3 study testing:➡️ Golcadomide + Rituximab versus➡️ Standard treatments chosen by the doctor (including rituximab + lenalidomide or chemotherapy). About 400 patients worldwide will take part.

What makes this trial particularly exciting:

• ✓ Oral treatment: Golcadomide is a pill taken at home, no IV infusions

• ✓ Fixed duration: 12 cycles total, not indefinite treatment

• ✓ Chemotherapy-free: No traditional chemo side effects

• ✓ Outpatient care: Maintain daily routines and quality of life

Patients will be followed for up to 5 years, measuring not only how long the cancer stays away, but also quality of life, time to next treatment, and minimal residual disease using advanced ctDNA technology.

Why This Matters for Patients?

Earlier studies of Golcadomide showed:

• High response rates

• Deep remissions in some patients

• Activity even after multiple prior treatments

• A manageable side-effect profile

  
  

If successful, GOLSEEK-4 could offer patients:

• ✔ A new option after relapse

• ✔ A treatment that supports the immune system

• ✔ A chemotherapy-free approach

• ✔ More flexibility and better quality of life

________________________________________

Final Thought

For the follicular lymphoma community, Golcadomide represents a new category of treatment that could fill a critical gap, offering strong effectiveness with better tolerability. That balance matters enormously when facing a chronic, relapsing disease.

This isn’t about false hope. It’s about scientific innovation creating better options. Every patient deserves treatments that not only work, but also allow them to live their lives with dignity and minimal disruption.

The GOLSEEK-4 trial began enrollment in July 2025. If you or someone you know may be eligible, talk to your oncologist about whether this trial could be an option.

You can also check eligibility via CancerBot here:👉 https://app.cancerbot.org/t/NCT06911502 (The link includes the NCT number for easy reference by clinicians and patients.)

The fight against cancer is won one breakthrough at a time … and Golcadomide may be an important step forward.