Matthew J. Matasar, MD

Question

What is your strategy for communicating with patients about the general efficacy of drugs that exist to treat classical Hodgkin lymphoma?

Answer

Conversations with patients with a diagnosis of classical Hodgkin lymphoma always include discussions of the available treatments ― which includes both the effectiveness as well as the potential risks. It is important to contextualize the likelihood of success of the approaches being discussed; this can be done in terms of likelihoods, in terms of expectations, or in terms of best-worst-most-likely outcomes. An example of a discussion with a patient in terms of likelihoods would be something to the effect of: “In a room of 10 people with disease like yours, if they were to receive this treatment, 7 or 8 of them would be cured; of the other 2 or 3, we would expect 1 or 2 of them to be cured with a second course of treatment, and we would only expect maybe 1 of the 10 of you to die from complications of Hodgkin lymphoma over the next 10 years.” An example of a discussion around expectations is as follows: “When we describe the side effects of treatments, we can divide them up into those that everyone experiences, those that many will experience, and those that are rare, but still important to understand.” Lastly, an example of a discussion in terms of best-worst-most-likely is: “If we were to give this treatment, the best case scenario is that you could be in remission for many years or perhaps even cured; the worst case scenario is that the treatment would not work to shrink your lymphoma or that you might even have bad side-effects from the treatment; the most likely scenario is that the treatment will work, but that it will only keep your lymphoma in remission for a few years.”

Question

Please explain how cell-free DNA (cfDNA) and/or circulating tumor (ctDNA) can be used to detect mutations in classical Hodgkin lymphoma. From your perspective, how far along is the science in this field for lymphoma, and is further research needed?

Answer

Techniques to analyze cell-free and circulating tumor DNA are rapidly evolving and being developed as techniques to predict or evaluate response to treatment, identify relapse, even guide decision-making on duration or intensity of treatment. This is more challenging in Hodgkin lymphoma, in which relatively fewer cancer cells are present, in fact, even in large lymph node masses caused by the lymphoma, relatively few cancer cells are present. This said, we are making strides in using these advanced technologies in managing Hodgkin lymphoma, both at Memorial Sloan Kettering Cancer Center and around the world. However, far more work is needed before these techniques can be used as part of the routine management of Hodgkin lymphoma.

Question

What are the most promising trials in classical Hodgkin lymphoma that are under way? Are there areas in which you feel more research should be directed?

Answer

There is a tremendous range of work being done to improve outcomes in classical Hodgkin lymphoma. For patients with newly diagnosed Hodgkin lymphoma, we continue to seek more effective and less toxic treatments. Critically important is in selecting who needs treatment beyond the traditional chemotherapy program of doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) chemotherapy, using biological predictive models and response-adapted trials (judging the quality of response to ABVD chemotherapy) to attempt to identify those relatively few patients who may need other therapeutic approaches. We are still learning just how powerful immunotherapy can be in Hodgkin lymphoma; we have two US Food and Drug Administration (FDA)-approved immunotherapies for patients with relapsed disease, but we need to understand if we should be using immunotherapy as part of first-line treatment and, if so, in which patients. For patients with relapsed disease, we are working to continue to develop our ability to use immunotherapy – combining immunotherapy drugs with chemotherapy, other immunotherapies, as well as developing new immunotherapy approaches such as cellular therapies and novel antibodies. The last area of research that remains a critically unmet need is in lymphoma survivorship. As we continue to cure more and more patients of Hodgkin lymphoma, we have a growing number of people living who have been cured of Hodgkin lymphoma who need specialized health care to monitor for and reduce the risk of late effects of the treatments they received. Clinical research and clinical trials identifying how best to care for our survivors are critically important.

Question

Autoimmunity-associated lymphoma: What are the trends in this space, and do you expect to see a rise in the incidence of this cancer subgroup? Could immunotherapies for other diseases/cancers affect incidence levels?

Answer

It has long been recognized that lymphoma risk is elevated in people with certain autoimmune diseases, including rheumatoid arthritis, inflammatory bowel disease, and other rheumatologic disorders. These risks appear to be related to the autoimmune disease itself, although certain treatments used in the management of rheumatologic diseases may contribute additional risk. Thankfully we have not yet seen a marked increase in the risk of lymphoma among patients treated with immunotherapy for other cancers, although there are case-reports emerging of just this phenomenon. As a discipline, we have a responsibility to remain vigilant for such potential complications, but the risks as we understand them now certainly would not lead me to recommend against giving optimal therapy – potentially including immunotherapy – for a cancer in need of treatment.

Question

Where is the field going for non-Hodgkin lymphoma (NHL) and T-cell lymphomas? What are exiting new and/or emerging therapies? Do you think chemotherapy will remain the standard frontline therapy in the near future?

Answer

We have seen a remarkably quickened pace of clinical trial and drug development in the treatment of T-cell lymphoma (as well as in non-Hodgkin lymphoma overall) during the last 5 years. We have our first program FDA-approved for newly diagnosed T-cell lymphoma, specifically for lymphoma expressing CD30, namely brentuximab vedotin and cyclophosphamide, doxorubicin, and prednisone (BV+CHP), as reported in the ECHELON-2 trial. In relapsed T-cell lymphomas, understanding of disease biology is informing development of targeted and biologic therapies, including histone deacetylase inhibitors, agents targeting PI3k-gamma, as well as immunotherapies. Our hope is that we can improve treatment further both for newly diagnosed and relapsed patients, most likely by combining effective novel therapies with proven chemotherapies.