Understanding the Evolution of Waldenström Macroglobulinemia Treatment

The treatment landscape for patients with Waldenström macroglobulinemia (WM) has evolved significantly in recent years, reflecting a more nuanced and patient-specific approach, according to Dr. Shirley D’Sa, who added that these new approaches have evolved from chemotherapy to chemoimmunotherapy and targeted therapies like BTK inhibitors.

To further delve into this topic, D’Sa, a consultant hematologist and clinical lead for the University College London (UCL) Hospital Centre for Waldenström’s Macroglobulinemia and Associated Disorders, sat down for an interview with CURE to discuss how treatment strategies for WM have evolved over the course of her career.

D’Sa also serves as an honorary associate professor at the UCL Cancer Institute. She also serves as the hematological lead in the joint neurohematology service at the National Hospital for Neurology, in Queen Square, London.

Transcript:

CURE: How have treatment strategies for WM evolved over the course of your career?

D'Sa: Over the years, it's been great; it's been great to witness the developments because, in the beginning, there was just a handful of chemotherapy treatments which, while quite effective in themselves, were also very toxic. The addition of Rituxan (rituximab), an antibody against CD20 found on B cells, which form part of WM, was a help and contributed to the improvement in outcomes. As time went on, in my own practice, we moved a little bit away from medicines like fludarabine. We actually did a number of high-dose chemotherapy treatments in some younger patients, like autologous stem cell transplants, and we tried to focus that treatment on those who were younger and had high-risk WM based on its biological behavior.

One has to bear in mind that back then, there were no targeted therapies for WM, so we had to make the most of chemoimmunotherapy. Regarding immunotherapy or Rituxan, that brings its own challenges, and over the years, we learned through investigators across the globe, notably the Boston group under Stephen Treon, about phenomena such as the Rituxan flare that occurs if IgM is raised and you give Rituxan, potentially causing a quite acute flare, which can lead to hyperviscosity.

So, over the years, we've nuanced the approach to managing WM by using different treatments in a more targeted and careful way, trying to circumvent potential complications. And of course, recently, I would say in the last 10 years, there's been the introduction and advent of targeted therapies, including BTK inhibitors.

At our center, we were involved from the early stages in trials of Imbruvica (ibrutinib) and also Brukinsa (zanubrutinib), both of which have proven to be extremely effective treatments. So yeah, it's been an interesting evolution throughout my career as a specialist because the disease area took off. There was also the gathering of an amazing community of physicians and researchers that continues to this day. And it's such a pleasure to be involved in that group because we work well together, and because WM is a rare disease, it's super important for that to happen.

Transcript has been edited for clarity and conciseness.

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