A recent study conducted by researchers at BC Cancer has shed light on the cause behind the different outcomes of patients with diffuse large B-cell lymphoma (DLBCL) who experience a relapse of their disease. The study, led by Dr. Laura Hilton, staff scientist at BC Cancer’s Centre for Lymphoid Cancer (CLC), and Dr. David Scott, clinical director of the CLC, aimed to understand the molecular characteristics of the initial diagnostic and relapse tumour samples of patients with DLBCL.

The study, published in the Journal of Clinical Oncology, confirmed that patients whose cancer relapses shortly after treatment typically have poor responses to additional chemotherapy-based treatment. However, when the relapse occurs more than two years from the time of diagnosis, the outcomes to chemotherapy are significantly better.

"We compared the genomes of the relapse DLBCL tumours against the diagnostic tumours," says Dr. Hilton. "What we found was that in people who experienced a late relapse, the two tumours were genetically very distinct, while in patients with an early relapse the two tumours were nearly identical. This suggests that resistance to treatment in early relapses is already present at the time of diagnosis, which explains why these patients have limited benefit from further chemotherapy after relapse. On the other hand, late relapses are effectively new tumours that are treatment naïve and still sensitive to further chemotherapy. ”

DLBCL is the most common type of lymphoma, with approximately 300 cases diagnosed each year in British Columbia and around 100 patients experience relapse annually.

The study's significance is underscored by the experiences of patients like Johanna J, a BC Cancer patient who was diagnosed with DLBCL in 2012.

"After more than 8 years, thinking I had been cured, I had a recurrence which left me feeling very anxious," she shares. "My oncologist elected to treat my late relapse with the same chemo regimen as was used the first time. I responded effectively once again. This recurrence happened two years ago, and I continue to be cancer-free to this day."

Johanna's experience aligns with the Dr. Hilton's findings, explaining why her relapsed lymphoma responded so well to chemotherapy again. It provides crucial insights into the underlying biological reasons for the differences in response between early and late relapse cases. Traditionally, chemotherapy-based treatments have been the standard of care for DLBCL patients who relapse. However, recent studies have shown that CAR-T cell therapy can significantly improve outcomes for patients with early relapse. Understanding the causes of resistance and the differences between patient subgroups can help tailor treatment approaches and ultimately improve outcomes.

Moving forward, Dr. Hilton plans to focus on patients with early relapse to further understand treatment resistance and identify more effective therapies. She also aims to explore the common precursor cells that contribute to the development of DLBCL and their role in determining how patients will respond to a range of different treatments.

The insights gained from this study have far-reaching implications, influencing the design of clinical trials and the development of targeted therapies. By distinguishing between different patient populations, researchers can better assess treatment efficacy and develop personalized approaches for improved outcomes. Ultimately, this research brings researchers and clinicians closer to developing more effective and tailored treatments for DLBCL patients.

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