How can treatment strategies evolve to address the challenges in chronic lymphocytic leukemia?

Cancer. It’s a formidable foe. For some patients, cancer can strike suddenly and progress rapidly. For others, their cancer may grow slowly over a longer timeframe. While a diagnosis of slow-progressing cancers may appear to be more readily treatable, they often come with different challenges. Patients must manage their chronic condition and balance ongoing treatment with the desire to live a fulfilling life, free from the constant anxiety of living with cancer.

This contrast can lead to a physical and emotional burden as profound as that of more aggressive cancers – and defines the chronic lymphocytic leukemia (CLL) experience. While it can be progressive and life-threatening, CLL typically grows slowly and is considered by many an indolent condition. Despite the slow progression, the constant threat of the disease looms large, making it difficult for patients to stay a step ahead – and leaving them feeling fearful and uncertain.

In recent years, targeted therapies have transformed the treatment of CLL, offering more durable outcomes and fewer, more manageable side effects. But despite these advances, challenges remain.

Translating insight into innovation

For more than 30 years, Stephan Stilgenbauer, MD, has seen these challenges first-hand through clinical practice and research. Today, he is Professor of Medicine and Medical Director of the Comprehensive Cancer Center Ulm (CCCU), Head of the Early Clinical Trials Unit (ECTU), and Head of the Division of CLL Dept. of Internal Medicine III at Ulm University in Germany.

“I’ve witnessed firsthand the duality of CLL – how a slow-moving cancer can cast a long shadow over a patient’s life,” he shared. “Patients want to be free of the disease, but that freedom can look different for everyone. We’ve made important strides, but we must still prioritize durable disease control while addressing the everyday realities patients face over time.”

Addressing CLL over the long term requires strategies that enable sustained treatment effect while minimizing side effects and day-to-day disruptions. Companies like BeOne Medicines, formerly known as BeiGene, Ltd., are focused on changing the landscape to deliver transformative medicines to more patients around the world.

“CLL is not just another cancer—it demands a distinctly different approach,” said Remus Vezan, MD, PhD, Vice President, Global Clinical Development, Hematology, BeOne.

Since its inception 15 years ago, BeOne has focused on researching and developing next-generation targeted therapies – for blood cancers like CLL, and other cancers – with the goal of not only extending life, but also improving quality of life.

Realizing the full potential of continuous therapy

Some patients consider ongoing therapy the optimal approach, offering a sense of freedom and peace of mind that they are actively managing CLL every day.

Zanubrutinib, an oral, next-generation BTK inhibitor, has emerged as a compelling option – particularly for patients with CLL who need or prefer the reassurance of continuous therapy to actively manage their disease.

Five-year follow-up results from the Phase 3 SEQUOIA trial of zanubrutinib in patients with treatment-naïve chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) without del(17p) highlight the therapy’s long-term impact, demonstrating continued progression-free survival and a reduced risk of disease progression compared to a mainstay chemoimmunotherapy (bendamustine-rituximab). Notably, the results from this study showed benefit for patients with unmutated immunoglobulin heavy-chain variable region (IGHV), a marker of more aggressive CLL. The study showed the safety profile of zanubrutinib was consistent with the results of prior studies with no new safety signals. The most common Grade ≥3 adverse events for zanubrutinib (greater than 10%) were neutropenia and hypertension.

Driving what’s next

While some patients find freedom in continuous treatment, others seek a different kind of freedom that comes from time-limited, also known as fixed-duration, regimens that are followed by a treatment-free period. But today’s fixed-duration approaches may have limitations, especially for patients with high-risk disease: their effect can deteriorate over time, and the disease eventually returns after treatment has stopped.

Finding the right balance between treatment duration and sustained efficacy remains a challenge. Exploring potential fixed-duration combinations with the goal of delivering lasting remission and reducing the likelihood of recurrence after treatment ends is a top research priority.

At BeOne, this next phase of research is exploring a regimen that includes BTK inhibition with its next-generation, highly selective, and pharmacologically potent BCL2 inhibitor. Designed to improve the safety and utility of this drug class, this asset aims to deliver deeper and more durable responses. BeOne recently announced it had completed enrollment in its ongoing registrational Phase 3 fixed-duration CELESTIAL-TNCLL study (NCT06073821), evaluating this combination in previously untreated CLL patients. In addition, it presented updated data at the 30^th European Hematology Association Congress (EHA 2025) from its ongoing Phase 1 study in R/R CLL, showing deep and durable responses.

“By combining sustained BTK inhibition with targeted BCL2 therapy, there is potential to achieve higher rates of undetectable minimal residual disease and longer-lasting remissions, all without the need for ongoing treatment,” said Prof. Stilgenbauer.

Shaping the future of CLL care

With advances in both continuous and fixed-duration therapies, the treatment of CLL is evolving to better reflect the needs and goals of patients. Whether it’s the reassurance of daily treatment or the freedom of time-limited therapy, the future of CLL care is rooted in choice, flexibility, and deeper, more durable responses.

“The fundamental goal for many patients is simple – to be free of disease – or just to “be”. And indeed, that aspiration is reflected in our company’s name – BeOne – and is at the core of our identity,” said Lai Wang, Global Head of R&D, BeOne. “It’s what drives us to develop therapies that empower each person with CLL to navigate treatment – and live their life – on their own terms.”

For more information about ongoing research in CLL, click here.