A study conducted by a group of Cleveland Clinic researchers led by medical oncologist Brian T. Hill, MD, PhD, found no reduction in overall survival (OS) for patients with nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) who underwent active surveillance compared to those who received initial frontline therapy. This is the largest study of patients with NLPHL to date with potential long-term implications on the management of this rare type of lymphoma.
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NLPHL is a rare form of Hodgkin lymphoma characterized by an indolent clinical course. It accounts for approximately 5% of all Hodgkin lymphoma cases. Although the treatment of NLPHL is similar to classical Hodgkin lymphoma and often involves radiation, chemotherapy or a combination of systemic therapies, it is not clear that immediate treatment at the time of diagnosis is needed for all patients.
“NLPHL tumor cells express CD20, unlike classical Hodgkin lymphoma, so when systemic treatment is given, it often utilizes rituximab in addition to other systemic agents,” Dr. Hill explains. “But, there are also many cases that can present with an isolated stage 1 lesion or lymph node…which are highly responsive to involved site radiation therapy. So, there are different treatment options [for NLPHL] that are largely dictated by the stage of lymphoma as well as the age of the patient.”
A proportion of patients with NLPHL will die due to acute treatment-related toxicity. Thus, serious adverse events and secondary malignancies remain a major concern with available therapies. Emerging evidence from clinical studies suggests that some patients with NLPHL may be safely managed with active surveillance only.
“The watch-and-wait approach is familiar to oncologists and many patients with indolent non-Hodgkin lymphoma,” Dr. Hill says. “For other diseases, such as follicular lymphoma, we do not always immediately treat the lymphoma just based on the diagnosis. Rather, we monitor for an indication for therapy.”
To investigate the feasibility of this approach in NLPHL, a group of Cleveland Clinic researchers including a student from the Lerner College of Medicine, Victoria Rogness, examined a large cohort of NLPHL patients who either underwent initial treatment, received no treatment or were managed with active surveillance. The study included data from the National Cancer Database about 2,490 patients with NLPHL who were diagnosed between 2010 and 2015. Of these 2,480 patients, 93.1% underwent initial treatment, 4.15% received no treatment and 2.74% underwent active surveillance. Most patients were male and presented with stage 1 or 2 disease.
“The National Cancer Database captures information on the initial therapy that was administered, whether it is surgery, radiation or systemic treatment, or in some cases no treatment,” Dr. Hills says. “What we found is that a proportion of patients with NLPHL were not immediately treated and were just monitored, and their overall survival was no different from those who had immediate chemotherapy treatment. Of course, we do not have a lot of details on those cases in this database, but this is consistent with what was reported from a single center series from Memorial Sloan Kettering in which investigators also observed that a subset of patients can safely be monitored without immediate treatment for their NLPHL.”
Dr. Hill and his collaborators found that OS was 94.2% for patients who underwent initial treatment, 89.3% for patients who had no treatment and 91.2% for patients who were managed with active surveillance. Moreover, the univariate analysis found no significant difference in OS between initial treatment and active surveillance groups; however, there was a significant difference in OS of patients who received treatment compared to those who did not receive treatment (hazard ratio, 2.87).
Dr. Hill is optimistic that this type of study, along with other observational cohorts, will “contribute to the recognition that not all patients with this diagnosis must be treated immediately, and that, in appropriately selected patients, active surveillance is a reasonable option and does not appear to compromise overall survival.”
He adds that active surveillance is already outlined as an option in treatment guidelines for NLPHL, but that it may not be commonly adopted by clinicians who do not see a large number of patients with NLPHL.
“This type of study will hopefully support the approach of active surveillance in a subset of patients [with nodular lymphocyte-predominant Hodgkin lymphoma],” he says. Potential benefits of not being treated immediately include “a decrease in the morbidity of therapy and [treatment] cost and the potential for late effects or secondary malignancies from radiation or chemotherapy.”
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