Radford Discusses Future of Novel Therapies in Non-Hodgkin Lymphoma

John Radford, MD

Several novel agents, including idelalisib (Zydelig), belinostat (Beleodaq), and ibrutinib (Imbruvica), have shown promise across multiple types of non-Hodgkin lymphoma (NHL). These new therapies, among others, have changed the treatment paradigm for NHL, significantly improving outcomes for patients.

John Radford, MD, Teenage Cancer Trust Professor of Teenage and Young Adult Cancer at the University of Manchester and Director of Research at the Christie NHS Foundation Trust, has focused his research on new treatments of lymphoma and monitoring their efficacy using novel biomarkers and the late effects of both standard and novel treatments in NHL.

In an interview with OncLive, Radford discusses the impact of these agents and what continued research is necessary to overcome treatment challenges.

OncLive: Novel agents, such as PI3 kinase and BTK inhibitors, are showing promise. What impact could they potentially have in NHL?

Dr Radford: There is already evidence of progress. There was a study published in The Journal of New England Medicine this year, which examined ibrutinib in patients with mantle cell lymphoma, which resulted in an unprecedented response rate in this difficult-to-treat population. These novel agents are being used in the relapse and refractory setting with very exciting results. There are many molecules that are being developed that show promise. There is no doubt that these novel agents will be practice changing worldwide.

These therapies are relatively new. What could the long-term side effects/impacts of these treatments be?

That is something that we need to be very much aware of. What is encouraging, however, is that many of these drugs, including ibrutinib, are so well tolerated. We have a number of patients that have been on this drug for a long time and in their words, “they don’t even notice they are taking it.” They are well and disease-free, and we just hope that continues.

However, we do need to think about the late effects of these new therapies. We don’t know what they are right now, and they need to be studied. In the short-to-medium term, they seem to be pretty well tolerated at the present time.

In terms of toxicity, how could newer agents compare with standard chemotherapy regimens, such as R-CHOP?

One of the problems with traditional chemotherapy is that it is very nonspecific. It is not targeted at a tumor, it is targeted at tissue and that leads to undesirable toxicities. With R-CHOP, the biggest problem is its impact on the heart. It is extremely desirable to find alternatives to these therapies. These newer agents could offer that.

What role could biomarkers play in determining the best treatment for patients with NHL?

Biomarkers are very important and are something that we desperately need. Molecular subtyping of the disease is also critical. For example, within diffuse large B-cell lymphoma, molecular subtyping is very important. We know that the activated B-cell subtype (ABC) has an inferior outcome to the GCB subtype. Therefore, the stratification of patients and then identifying which therapies work best for which patients is very important. Identifying biomarkers to predict whether or not someone is going to respond will be helpful, because many of these drugs are very expensive and we need to be smarter about how we use them. We need to target those patients who really can benefit and not those who don’t.

Are there any studies in NHL for which you are anticipating the results?

Here in the United Kingdom, we have a very interesting study called Randomised Evaluation of Molecular Guided Therapy for Diffuse Large B-cell Lymphoma With Bortezomib (REMoDL-B). This should be completing recruitment shortly. In that study, we have real-time gene expression profiling being applied at the time of diagnosis. That will be a very important study to see if that genotyping exercise is actually of clinical utility.

Another study that is going to be very interesting is the PHOENIX study. In this study, patients with the ABC subtype are randomized between R-CHOP plus placebo or R-CHOP plus ibrutinib. This will show us if the addition of ibrutinib improves the outcomes for this poor prognostic group.

I am also interested in the IELSG 32 study, which looks at CNS lymphoma. This is a very difficult-to-treat entity. I think the results of that study are going to be very important for the ongoing treatment of CNS lymphoma.