Raising the bar in haematology drug development

Nancy Valente provides a look at how Roche’s innovation, heritage and scientific focus help drive significant advances in haematology, one of the more diverse and challenging areas of medicine.

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Nancy Valente, VP Global Product Development Haematology/Oncology at Roche/Genentech.

It was a personal family experience that influenced the career path I took into medicine, and I have been fortunate enough to be in a role that helps make a difference for people who have very serious illnesses. From my time working in haematology, across blood cancers such as leukaemia and lymphoma, and bleeding disorders such as haemophilia, I know only too well how complex and difficult this branch of medicine can be.  

Striving to make a difference

At Roche our research efforts focus on areas where there is most clinical need. We look to make a difference for people with diseases where current treatment options are limited, where there is a need to improve the cure rates, or where remission periods could be extended giving people more time without illness, and a better quality of life during that time. One key aspect of our approach is that we are always anchored to understanding the science and the biology of disease to drive the development of our medicines. This philosophy is entrenched in our heritage and evident in our approach to clinical trials in haematology so far.

We always strive to raise the bar in an effort to develop medicines that have the potential to transform treatment. This means challenging the standard of care, even if it’s one of our own medicines.

One specific example is the work we are doing in non-Hodgkin lymphoma, or NHL, a very diverse and distinct group of blood cancers affecting white blood cells known as lymphocytes. Much of our recent research focus has been on advancing patient outcomes for two of the most common types of NHL, follicular lymphoma and diffuse large B-cell lymphoma, or DLBCL. While both are B-cell lymphomas, they are quite different in presentation and the course each disease takes.

Diffuse large B-cell lymphoma accounts for 30% of new non-Hodgkin lymphoma diagnoses.
Diffuse large B-cell lymphoma accounts for 30% of new non-Hodgkin lymphoma diagnoses.

Taking a closer look at DLBCL, which accounts for 30% of new NHL diagnoses, we know that it occurs primarily in older people, the first signs of disease generally being enlarged lymph nodes with symptoms such as unexplained weight loss, fever and night sweats. Due to its aggressive nature, DLBCL requires prompt treatment. As many as 60% of people can be cured with the current standard of care treatment, but for those who are not, the disease often progresses rapidly. A key aim of our research has been to improve cure rates achieved with first line treatment. Therapies that are effective for people who have relapsed following treatment are also needed.

Looking to the future

Efforts in this area have not been without challenges. Since the transformational introduction of monoclonal antibodies in haematology some 20 years ago, there has been very little advancement in the treatment of DLBCL. A number of recent DLBCL studies have reported mixed results, and despite our high expectation, one of these studies was one of our own phase III trials. We are fortunate that the robustness of that study design and conduct of that trial mean we will have a wealth of data and insights that will help us develop the next wave of potential medicines for this aggressive disease. Current standard of care treatment with chemo-immunotherapy has been shown to be very effective and has set a high bar to be improved upon, but we remain undeterred. The key will be to find a way to identify which patients do not benefit from current treatment and to better understand the biology of their particular disease.

As our understanding of the biology of DLBCL continues to grow, we need to adapt our thinking about how to advance treatment. One area the haematology community is starting to understand more is how different DLBCL subtypes categorised by the cancer cell of origin, either a germinal centre B-cell or activated B-cell, respond to certain treatments. Beyond that, emerging biomarkers such as Myc or BCL-2 may be important to predict how patients may respond to certain medicines, regardless of cancer cell of origin. Through continued research, we may even find that patients could benefit from an approach that combines individualised therapy based on their specific gene mutations and new approaches to targeting CD20 (a key marker of B-cells); or that innovative approaches such as antibody directed chemotherapy or immunotherapy are a better way to target CD20.

We continue to explore the potential of innovative medicines for the treatment of this disease. To remain successful in this area takes dedicated teamwork and collaboration, and a continued focus on the science and biology of the disease. I’m proud to be part of a team that strives to deliver the insight that will help direct our research efforts and make a difference for patients every single day.