Golcadomide for Aggressive Lymphoma

Patients with diffuse large B-cell lymphoma (DLBCL) can experience relapse after undergoing initial treatments, making the development of new therapies critical. A recent study highlights promising results for GOLCA, a first-in-class cereblon E3 ligase modulating drug (CELMoD) designed to treat lymphoma. 

What is GOLCA?

GOLCA (full name golcadomide, Bristol Myers Squibb) targets two proteins, Ikaros and Aiolos, that promote immune system activation, have direct anti-tumor effects, and are mainly distributed in lymphoid tissues. Preclinical studies suggest GOLCA is 100 times more effective at halting tumor cell growth and inducing programmed cell death in DLBCL compared to existing immunomodulatory agents such as lenalidomide (Revlimid, BMS).

First-in-Human Study of GOLCA 

This study evaluated whether GOLCA is safe and works for treating patients with DLBCL whose disease stopped responding to treatment or returned after a period in remission (relapsed or refractory). This study explored different doses of GOLCA and the possible combination with rituximab. The latest findings focus on the long-term results of combining GOLCA and rituximab.

The study evaluated 65 patients with relapsed or refractory DLBCL, with a median age of 66 (ranging from 20 to 86). These patients had received a median of four previous anti-cancer therapies, including CAR T-cell therapy and bispecific antibodies. 

Side Effects of GOLCA When Combined With Rituximab

The treatment was generally well-tolerated; the most commonly reported side effects were neutropenia (low white blood cell count) in 61% of patients and anemia in 38%. To manage these side effects, patients received granulocyte-colony stimulating factor (G-CSF), which helps boost white blood cell production. 

Effectiveness of GOLCA Plus Rituximab

Among the 65 patients who were evaluated for treatment response, the results showed that a higher dose had better outcomes: 

• The overall response rate was 33% in those receiving the 0.2 mg dose and 59% in those receiving 0.4 mg

• Those who responded started to show signs of remission between 1.5 and 3 months after starting treatment, and for the majority, the response lasted for over 5.5 months; though five patients had durable responses lasting over a year 

Importantly, patients with prior exposure to CAR T-cell and bispecific antibody therapies also responded to this treatment, making it a promising option for those with limited alternatives.

You can read more about golcadomide combinations by clicking the button below. Here, we cover the promising phase 1 results of golcadomide combined with R-CHOP for newly diagnosed patients. 

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Achieving MRD Negativity in High-Risk and Aggressive Lymphoma  

This phase 3 study of golcadomide+R-CHOP continuation of the phase 1 results GOLSEEK-1 trial (still recruiting). 

GOLSEEK-1 Phase 1 Trial 

This study is an ongoing multicenter, open-label study focusing on patients newly diagnosed with aggressive B-cell lymphoma. The primary objective is to assess the safety of GOLCA at different dosing levels, while secondary goals include evaluating its effectiveness and analyzing tumor DNA changes over time.

• This trial used six cycles of golcadomide + R-CHOP versus only R-CHOP, and 85% high-risk patients had their disease controlled or in remission 1 year after starting the treatment with GOLCA.

• It has predictable and manageable safety in patients with untreated aggressive B-cell lymphoma.

• Treatment with 0.4 mg of golcadomide appears to overcome molecular high risk, resulting in high rates of minimal residual disease (MRD) negativity, which is liked with greater odds of longer remissions.

We interviewed Dr. Julio Chavez at the American Society of Hematology conference, one of the researchers and presenters of this study. He shared relevant insights from the study, highlighting why research in high-risk and aggressive lymphoma types is crucial. 

This study highlights the promising efficacy of GOLCA, particularly at the 0.4 mg dose level, in improving progression-free survival and achieving MRD negativity. The data suggest that this regimen may be particularly beneficial for patients with high-risk genetic features. 

A larger, phase 3 randomized trial, GOLSEEK-1, will further investigate these findings and explore the role of MRD status in guiding treatment decisions. This study is still recruiting and you can check your eligibility in our Clinical Trial Finder.  We will cover the updated results at HealthTree, so stay tuned on our news site to read all updates. 

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Summary

The findings from recent studies show the potential of golcadomide as a breakthrough treatment for DLBCL, especially in high-risk patients. Its combination with R-CHOP has demonstrated a significant improvement in progression-free survival, with an 86% rate in aggressive cases. Additionally, its ability to achieve MRD negativity suggests it could help overcome molecular high-risk. With the ongoing GOLSEEK-1 trial further evaluating its efficacy, golcadomide may become a crucial addition to treatment strategies for relapsed and high-risk lymphoma patients.