Though Hodgkin lymphoma is highly curable, its late effects can be costly financially and in terms of survivor quality of life. Cost-per-death analyses show it has the second-highest cost per death or lost-productivity cost (Int J Cancer 2015;136:E136-E145). And productivity analyses of cancer mortality have shown Hodgkin lymphoma to be the second most costly cancer in terms of lost lifetime earnings (J Natl Cancer Inst 2008;24:1763-1770).
The high rates of late effects are due to increased incidence of cardiovascular disease, second malignant neoplasms, and other prominent treatment-induced morbidities that may result in excess morbidity and early mortality, explained Andrew Evens, DO, MSc, Director of the Lymphoma Program at Rutgers Cancer Institute of New Jersey. In a recent editorial in the Journal of Clinical Oncology, Evens and colleagues comment on a recent dataset that reveals a large number of patients experience side effects quite soon after treatment (J Clin Oncol 2020; doi: 10.1200/JCO.20.02668, 2020; doi: 10.1200/JCO.20.00264).
"There are many previous reports delineating the increased rate of late effects occurring more than 20-30 years after therapy," Evens noted. "However, [this recent] analysis shows that increases in treatment-related morbidity and early mortality occur within the first decade after therapy (and as early as 1 year) with modern, frontline therapy."
While this new data is important, Evens and his coauthors note that real-world data consisting of individual patient data must also be carefully culled and harmonized and put into flexible decision models so clinicians can learn from and translate that learned knowledge into practice for short-term and long-term outcomes for individual Hodgkin lymphoma patients. The benefits and risks of different therapies depend on several characteristics, including patient age, sex, and disease stage, among other factors.
Evens is a co-principal investigator for the HoLISTIC [Hodgkin Lymphoma International Study for Individual Care] consortium and is doing that work. He shared his thoughts with Oncology Times about the endeavor.
1 What interventions might lessen these crippling late effects of Hodgkin lymphoma?
"A critical consideration is to continue studies to delineate more individualized therapy for patients with Hodgkin lymphoma, [including] efforts to harmonize large amounts of individual patient-level data on efficacy and toxicity (acute, post-acute, and late) across varying treatment platforms that are applicable to diverse settings across the world to aid in decision-making. In addition, continued efforts are needed to examine the de-escalation of therapy for low-risk patients with Hodgkin lymphoma via response-adapted strategies and/or integration of targeted therapeutic agents.
"Efforts are underway to harmonize large amounts of individual patient-level data for patients with Hodgkin lymphoma treated in recent international clinical trials and from prominent cancer registries and survivorship cohorts. More breakthroughs are needed to aid with prognostication and prediction of therapy beyond early/interim PET response adaption, such as ctDNA and other technologies.
"The ongoing North American clinical trial, S1826 (NCT03907488), for advanced-stage classic Hodgkin lymphoma is examining a host of correlative scientific studies, as well as health outcomes, cost effectiveness, and health-related quality-of-life analyses."
2 Can you talk more about the work of the HoLISTIC consortium?
"[HoLISTIC researchers] are harmonizing detailed individual patient-level data from 15 large Hodgkin lymphoma clinical trials in the modern era of newly diagnosed Hodgkin lymphoma patients, as well as individual patient-level data from six large Hodgkin lymphoma registries-the latter considered more 'real-world data' and enriched with longer follow-up and crucial information on post-acute toxicities. Applying established data science methods, we have created a common data model with a data dictionary across all sources that will result in a detailed and fully annotated database of [approximately] 20,000 Hodgkin lymphoma patients.
"We will use predictive modeling and multi-state modeling that incorporates interim/early PET and tumor biology with varying treatment platforms to create simulation/decision modes. They will be designed to incorporate future prospective data as new/novel treatment that will delineate acute, post-acute, and late effects and outcomes for individual Hodgkin lymphoma patients. Importantly, this robust database has been designed to incorporate new studies and data and longer-term outcomes as they become available."
3 What is the ultimate message of this work?
"Providers should know that significant treatment-related toxicities and early mortality, such as heart disease, infections, lung disease, and second cancers, are seen with modern therapy and occur the first decade after treatment (and as early as 1 year after diagnosis). Currently, this should highlight the importance of survivorship for Hodgkin lymphoma patients, and the development of survivorship plans should be a critical part of each patient's post-therapy care within 1-2 years.
"Additionally, clinical studies leveraging more targeted therapeutics for Hodgkin lymphoma patients are ongoing and predictive modeling and data simulation efforts such as HoLISTIC and the pediatric cancer data commons are underway to harmonize data for Hodgkin lymphoma of all ages and geographies to aid with data standardization and create predictive tools that delineate short- and long-term outcomes across varying therapeutic strategies for individual Hodgkin lymphoma patients."