Hodgkin lymphoma: Improving short-, long-term risks of treatment
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Common treatments for Hodgkin lymphoma, such as radiation and chemotherapy, while effective, carry significant short- and long-term risks for patients.
Currently, oncologists are pursuing knowledge on how to best personalize Hodgkin lymphoma treatment for patients in order to reduce these risks without compromising their curative potential.
For instance, risks often associated with certain Hodgkin lymphoma treatments, including cardiac dysfunction and hypertension, may be linked to genetics, meaning not all patients undergoing Hodgkin lymphoma treatment are at equal risk for these conditions. Oncologists are currently exploring new treatments meant to minimize the use of radiation and spare patients the effects that can grow from traditional treatments.
In an interview with Healio, Matthew J. Matasar, MD, associate member of lymphoma service and medical director of lymphoma survivorship at Memorial Sloan Kettering Cancer Center, discussed changes, concerns and future promise regarding Hodgkin lymphoma treatment.
Healio: How have changes in treatment for classic Hodgkin lymphoma improved the risk for late effects of therapy?
Matasar: Over the last decade, we've really seen tremendous progress in the management of Hodgkin lymphoma. We've gone from an older era in which the goal of therapeutic development was to find more intensified approaches to the treatment of the underlying malignancy, which can then result in potentially increased short- and long-term risks.
But now we've come over to the other side of the mountain where we're really trying to pursue improvements in therapy by trying to learn how best to limit therapeutic exposures and how best to personalize the amount, extent and intensity of treatment. We're also leveraging novel therapeutics, which sometimes have less short- or long-term toxicity than standard cytotoxic chemotherapeutics to try to both improve our cure rates as well as to reduce the risks of short- and long-term effects.
Healio: What concerns about treatment-related effects still exist? Have new concerns emerged with the introduction of newer therapies?
Matasar: Survivors of Hodgkin lymphoma still remain at risk for late effects of therapy despite these advances, and when we think about late effects, it's usually in relation to the therapeutic exposures that were required, hopefully, to achieve cure. For Hodgkin lymphoma, anthracycline-based chemotherapy remains the standard of care for patients who are eligible for such treatment with newly diagnosed classical Hodgkin lymphoma,
and we know that there's a dose-response curve in terms of a risk for late-onset cardiomyopathy. A lot of earlier concerns, and concerns that persist now regarding late effects of Hodgkin therapy, however, are related to the use of radiation therapy as a consolidation for bulky or early-stage disease. Modern anti-Hodgkin lymphoma therapy really does tend to minimize the number of patients who require the use of radiation therapy as part of their first-line treatment, which then allows us to limit the potential long-term risks of radiation for many patients.
Healio: Do the risks for late effects differ among different subgroups of patients? For example, what role does age or disease stage play?
Matasar: Regarding anthracycline-based chemotherapy and the cardiac risks that are associated with it, we know that not everybody is at equal risk for anthracycline-associated cardiomyopathy. Now there are some genetic factors that are still being teased out by research groups, both at Memorial Sloan Kettering and around the world, but we know that there are other clinical factors that are associated with these risks, including baseline cardiac dysfunction and other cardiac comorbidities, most notably hypertension.
Healio: How can physicians help manage or mitigate these risks?
Matasar: The best that we can do as medical oncologists to limit delayed effects of therapies for Hodgkin lymphoma is really to be thoughtful about the selection of first-line therapy.
For patients aged older than 60 years who have underlying pulmonary dysfunction, it’s trying to select programs that don't incorporate bleomycin. For patients at elevated cardiac risk, this means being thoughtful about how to engage them in a survivorship program where you can do advanced cardiac monitoring, either yourselves or in collaboration with a survivorship clinic or cardio-oncologists. You try to identify patients who are experiencing early-onset cardiac dysfunction, which may present an opportunity to intervene to slow or reverse those changes.
For patients who have autoimmune disease that may put them at heightened risk for complications from checkpoint inhibitor therapy, partnering with our rheumatological colleagues and being cautious about the use of such agents is important. For patients with underlying neuropathy, or who may be at risk for severe neuropathy, this means being thoughtful about the use of brentuximab vedotin (Adcetris, Seagen), which is now FDA-approved as part of first-line therapy in addition to its previous usages in relapsed and refractory disease. So it really comes down to patient selection and making sure that you're thinking about individual patient risks regarding the treatment or that stem from the treatments before you start cycle one, day one.
Healio: Who should manage these patients with late effects of treatment? Should they receive care from a specialist, their primary care provider or at a survivorship clinic?
Matasar: I think that long-term survivors of Hodgkin lymphoma, particularly those treated with higher-risk programs, such as combined modality therapy, are really the ideal patients to benefit from a multi-modal, multidisciplinary survivorship care program. They incorporate the expertise of medical oncologists with training and survivorship care as well asadvanced-practice practitioners who have time and dedication to spend with their patients. And they can incorporate specialists from allied specialties, including cardio-oncology, pulmonology, rheumatology and infectious diseases — the host of specialties that we rely on when constructing a multidisciplinary care program around our complex survivors.
Healio: How can the oncologist best deliver this survivorship information to patients?
Matasar: It's long been recognized that survivorship care plans offer a unique benefit to our survivors, both in terms of informing them about their treatment and educating them about what optimal survivorship care would look like. Sharing is structured throughout your care plan with patients and patients’ other physicians and providers as a way both to empower the patient to seek out the best survivorship care possible as well as ensure that the entire care team built around that patient's care is on the same page and has an equal understanding of that patient's individualized risks and the best practices for safeguarding their health.
Healio: Are there any treatments in the pipeline or under investigation that show promise in addressing these concerns?
Matasar: In my mind, the best innovations right now in Hodgkin lymphoma for minimizing late effects are those that allow us to deliver more patients a cure with first-line therapy and limiting most toxic agents that we have traditionally relied upon to achieve cure.
These include novel therapies, such as antibody-drug conjugates and immunotherapeutic medications, that allow us to minimize reliance on cytotoxic chemotherapy and allow us to continue to further minimize the use of radiotherapy. In leveraging these newer medicines, we can spare patients the late effects associated with these known toxins.
Healio: What are the unmet needs in this area?
Matasar: There remains a significant amount of unmet need in the care of our Hodgkin lymphoma survivors. Investigators in the United States and globally have done an outstanding job of characterizing the burden of the disease and of late morbidity and mortality in our hospital survivors. What we really lack are effective interventions for patients who experience late effects or who have been found to be at ultra-high risk for complications. We lack evidence regarding successful interventions to either prevent or reverse these potentially life-threatening complications of therapy.
Healio: Is there anything you feel is important that you would like to add?
Matasar: One thing that I would add is that the work of studying survivorship care for Hodgkin lymphoma survivors remains a moving target because there is a natural lag between therapeutic advances and shifting and improving standards of care, and a clear understanding of late effects of those therapies. We need to continue to work as a discipline to follow our Hodgkin survivors to understand the late effects of our newer treatments as our survivors are cured and go on to live their lives.
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