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Moving Beyond Chemotherapy: How Biomarker Testing is Changing Cancer Care

By Brian Koffman, MDCM (retired), DCFP, FCFP, DABFP, MSEd and Dany Habr, M.D.

Nathan, who is living with CLL, and his family

Nathan, who is living with CLL, and his family

Sponsored by BeiGene

When Nathan was diagnosed with chronic lymphocytic leukemia (CLL) at just 45 years old, his world turned upside down overnight. As a military veteran and ER nurse, he was no stranger to facing challenges, but this was different. His local oncologist initially recommended chemotherapy without ordering biomarker testing—a decision that could have had devastating consequences for his prognosis.

Unsatisfied with the initial treatment plan, Nathan dove into research, sought new opinions and discovered the importance of understanding his unique biomarker status. This led him to a CLL specialist who ordered the necessary tests, uncovering critical information about his genetic profile and recommending a non-chemotherapy treatment that offered a potentially better outcome. Today, he is in remission and credits biomarker testing with not only transforming his treatment plan but also giving him hope for a healthier future.

Nathan’s story is a powerful example of the life-changing potential of biomarker testing. Yet, for many patients with CLL, his experience remains the exception rather than the rule. Bold scientific advances in cancer treatment have paved the way for more personalized approaches, allowing therapies to align with a patient’s unique biology. But many patients continue to face outdated treatments that fail to address the specific needs of their disease. This gap is especially significant in CLL / small lymphocytic lymphoma (SLL), the most common type of adult leukemia.1,2

CLL / SLL, a slow-growing but life-threatening blood cancer, accounts for one-third of all new leukemia cases diagnosed in adults each year.3,4 Despite significant progress in treatment options, many patients are still treated with chemotherapy—an approach that often comes with harsh side effects and limited effectiveness, especially for patients with a high-risk genetic profile.1 This reality persists even as biomarker testing, a powerful diagnostic tool, has evolved and provided the potential to guide patients and their doctors toward safer and more effective targeted therapies.1 Unfortunately, biomarker testing in CLL remains underutilized in community clinics.5

Why Biomarker Testing is a Game-Changer in CLL

Biomarker testing, conducted through a blood test, provides critical insights into a patient’s genetic profile, identifying molecular features that influence how well a treatment might work, and also helps predict how the disease may progress.1 For example, approximately 50% of CLL / SLL patients have high-risk molecular features that may limit the effectiveness of some treatments like chemotherapy and increase the likelihood of disease progression if not treated correctly.6,7

In fact, of those patients, about 10% of CLL / SLL patients have the high-risk del(17p) and/or TP53 mutation before starting treatment, and about 40% of patients will develop del(17p) and/or TP53 mutations after relapsing or not responding to treatment.8,9 Biomarker testing before starting treatment can help identify these features, enabling healthcare providers to guide patients toward more targeted therapies tailored to their needs, ultimately improving outcomes.1

What’s more, genetic profiles evolve over time, meaning a treatment that worked during an earlier stage of the disease may no longer be effective after progression.1 This reinforces the critical need for retesting at each stage to ensure that patients receive therapies aligned with their current disease biology.

Nathan and his wife, Lisa

Nathan and his wife, Lisa

Moving Beyond Chemotherapy to Targeted Therapies

For decades, chemotherapy was a go-to treatment for cancer, widely applied in a one-size-fits-all approach. While it has saved lives, it comes at a cost: significant toxicity, immunosuppression, and, for many CLL / SLL patients, limited effectiveness and poorer outcomes.10 High-risk patients with unmutated IGHV, del(17p) and/or TP53 are particularly vulnerable to poor outcomes with chemotherapy.1

Thankfully, the rapid pace of innovation in cancer research has paved the way for more precise treatments in CLL / SLL, including a shift toward more targeted therapies. National guidelines, such as those from the National Comprehensive Cancer Network®, now recommend the newer covalent Bruton’s tyrosine kinase (BTK) inhibitors or a B-cell lymphoma 2 (Bcl-2) inhibitor plus a monoclonal antibody over chemotherapy as preferred treatment for nearly all people with CLL / SLL.1,11 BTK inhibitors block a protein in cancerous B cells called Bruton’s tyrosine kinase, stopping signals that cause CLL / SLL growth.1 Bcl-2 inhibitors push CLL /SLL cells towards cell death or apoptosis. Monoclonal antibodies target cancer cells for destruction by the immune system. These targeted therapies, guided by biomarker testing, can align with the unique biology of each patient, offering potentially improved outcomes and fewer side effects.1

Biomarker testing also informs which targeted therapies are best suited for individual patients. For example, it can guide whether to use continuous treatment with a BTK inhibitor versus a fixed-duration regimen.1 In fact, patients with high-risk features like unmutated IGHV, TP53 and del(17p) may have better outcomes with a continuous treatment approach.12

A Call to Action in CLL / SLL Care: Test Before Treat

The benefits of biomarker testing should be a universal standard. To achieve this, testing and retesting before all treatments must become the norm—for all CLL / SLL patients, regardless of where they receive care.

For patients and caregivers, the message is clear: advocate for yourself. Ask your doctor about biomarker testing before starting each and every line of therapy or after disease progression. By understanding your unique genetic profile, you can ensure your treatment plan is tailored to your specific needs, just as Nathan did.

Biomarker testing is more than a diagnostic tool—it’s a gateway to more personalized care, a chemo-free future for many, and the key to unlocking potentially better outcomes and improved quality of life for countless CLL / SLL patients. The future of CLL / SLL treatment is here, and it begins when we Test Before Treat. Because as we say at CLL Society, “Smart Patients Get Smart Care.”

Brian Koffman, MDCM (retired), DCFP, FCFP, DABFP, MSEd, is Co-Founder, EVP, Chief Medical Officer at CLL Society, the world’s leading authority for CLL / SLL cancer patients. Dany Habr, M.D., is Head of Medical Affairs, North America & International Markets at BeiGene, a global oncology company developing targeted therapies for CLL / SLL.

Together, BeiGene and CLL Society are advancing Before Treat™, an awareness campaign to promoting biomarker testing to improve patient outcomes in CLL. Learn more at www.CLLTestBeforeTreat.org.

References:

  1. NCCN. (2024). NCCN Guidelines for Patients: Chronic Lymphocytic Leukemia. National Comprehensive Cancer Network. https://www.nccn.org/patients/guidelines/content/PDF/cll-patient.pdf
  2. Nguyen, T. T., Nhu, N. T., Tran, V. K., et al. (2023). Efficacy and Safety of Bruton Tyrosine Kinase Inhibitor Monotherapy Compared with Combination Therapy for Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma: A Systematic Review and Meta-Analysis. Cancers, 15(7), 1996. https://doi.org/10.3390/cancers15071996
  3. American Cancer Society. What is Chronic Lymphocytic Leukemia? Updated May 10, 2018. Accessed November 2024. https://www.cancer.org/cancer/types/chronic-lymphocytic-leukemia/about/what-is-cll.html
  4. American Cancer Society. Key Statistics for Chronic Lymphocytic Leukemia. Updated July 1, 2024. Accessed November 2024. https://www.cancer.org/cancer/types/chronic-lymphocytic-leukemia/about/key-statistics.html
  5. Mato, A. R., Barrientos, J. C., Ghosh, N., et al. (2020). Prognostic Testing and Treatment Patterns in Chronic Lymphocytic Leukemia in the Era of Novel Targeted Therapies: Results From the informCLL Registry. Clinical lymphoma, myeloma & leukemia, 20(3), 174–183.e3. https://doi.org/10.1016/j.clml.2019.10.009
  6. Leukemia and Lymphoma Society. Chronic Lymphocytic Leukemia. Revised June 2021. Accessed November 5, 2024. https://www.lls.org/sites/default/files/2021-07/PS34_CLL_Booklet_2021.pdf
  7. Döhner H., Stilgenbauer S., James M.R., et al. 11q deletions identify a new subset of B-cell chronic lymphocytic leukemia characterized by extensive nodal involvement and inferior prognosis. Blood. 1997;89(7):2516-2522.
  8. Griffin, R., Wiedmeier-Nutor, J.E., Parikh, S.A., et al. (2023). Differential prognosis of single and multiple TP53 abnormalities in high-count MBL and untreated CLL. Blood advances, 7(13), 3169–3179. https://doi.org/10.1182/bloodadvances.2022009040
  9. Brieghel, C., Aarup, K., Torp, M. H., et al. (2021). Clinical Outcomes in Patients with Multi-Hit TP53 Chronic Lymphocytic Leukemia Treated with Ibrutinib. Clinical Cancer Research, 27(16), 4531–4538. https://doi.org/10.1158/1078-0432.ccr-20-4890
  10. Iyer, P., & Wang, L. (2023). Emerging Therapies in CLL in the Era of Precision Medicine. Cancers, 15(5), 1583. https://doi.org/10.3390/cancers15051583
  11. Wierda, W. G., Brown, J., Abramson, J. S., et al. (2022). NCCN Guidelines® Insights: Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, Version 3.2022. Journal of the National Comprehensive Cancer Network: JNCCN, 20(6), 622–634. https://doi.org/10.6004/jnccn.2022.0031
  12. Tam, C., & Thompson, P. A. (2024). BTK inhibitors in CLL: Second-generation drugs and beyond. Blood Advances, 8(9), 2300–2309. https://doi.org/10.1182/bloodadvances.2023012221