Journal of Clinical Pathways spoke with Peter Martin, MD, Lymphoma Service Chief, Weill Cornell Medicine and New York-Presbyterian, about the role of targeted therapies and clinical pathways in shaping future treatment practices for marginal zone lymphoma (MZL).
Which treatment type (i.e. TKIs, immunotherapies, radiotherapy, etc.) do you believe will have the largest impact on MZL treatment in the next 10 years?
Given the role of chronic inflammation in the pathobiology of MZL, I suspect that therapies that are able to inhibit signaling through these pathways are likely to have the most impact over the next decade. These might include inhibitors of B-cell receptor signaling, the JAK/STAT pathway, toll-like receptor signaling, NOTCH signaling pathways, and others. Also, I think that the recent development of effective therapies for hepatitis C are likely to have a major impact on the outcomes of some patients with splenic MZL. Further down the road we may have a better understanding of some of the factors that drive marginal zone lymphomagenesis and will hopefully be able to intervene in ways that are analogous to the way we use H pylori eradication to treat gastric MALT lymphoma. Similarly, it’s interesting to think about the potential role that immune checkpoint inhibitors might have given their surprising activity in other cancers and some lymphoma subtypes, but the right combinations might take time to develop.
What do you believe will be the standard-of-care first-line therapy for MZL in the coming years?
I think that it depends largely on how far ahead you set your sites. MZL has been a very challenging disease to study because it is heterogeneous and uncommon, so that means that changes are slow and the current standard first-line therapies, observation, single-agent rituximab, or rituximab plus chemotherapy, will likely be standard for some time. The recent approval of ibrutinib in previously treated MZL offers a potential pathway to moving that forward in a subset of patients that might otherwise be treated with chemotherapy. It may take some time to move other drugs forward, but I’d love to be surprised.
What, if any, are the therapy options currently in the trial stages for MZL treatment?
There are very few drugs that are being developed specifically for MZL. Just looking through the latest clinical trials it’s easy to see that most trials are including MZL as part of the larger NHL cohort. The pathways that I mentioned are all under evaluation, so we will see more data in MZL emerging over the next few years.
Do you believe clinical pathways are adaptable for MZL treatment?
Sure, maybe to some degree. But it’s tough to capture the heterogeneity of MZL on a simple algorithm. For example, MALT lymphoma in the intestine is not the same as MALT lymphoma in the skin. It’s probably harder to capture the diversity of opinions about how MZL should be treated in the absence of large phase III trials. For example, a stage I MALT lymphoma might be managed differently in a 30-year-old than a 80-year-old, even if it is unlikely to impact longevity in either case. It might be hard to protect patients from over treatment that is described as appropriate management in a clinical pathway.
What is precision medicine’s influence on cutting-edge MZL treatment?
At this point I would have to say that precision medicine has little if any influence in the management of MZL. There are a handful of cases where whole exome sequencing or targeted sequencing might pick up an actionable mutation that could prompt a change in therapy, but not enough to say that precision medicine should guide initial treatment decisions or become a standard of care in the foreseeable future. That said, I think that we are now seeing several investigators describe the spectrum of known mutations in MZL, and we are seeing investigation of drugs that might target those pathways, so I can definitely imagine a future where precision medicine has a role.
