Role of Novel Therapies in Hodgkin Lymphoma

Radhakrishnan Ramchandren, MD: This is actually a very exciting time for Hodgkin lymphoma. There are a number of novel agents, and there are attempts that have shown the ability to reduce therapy in patients who are doing well or have early stage disease and intensify therapy in those patients with more aggressive disease. That has really been the holy grail of Hodgkin lymphoma. Largely, patients do well with ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine). However, a subset of patients doesn’t do well. In those patients who have favorable prognoses, long-term survivals are limited by toxicities associated with both chemotherapy and radiation.

Therefore, identifying new therapies and, now, risk-adaptive therapy has become important. In the future, I see a confluence of these 2 philosophies—we looked at risk, and we look at risk-adaptive therapies with novel agents. In the next 3 to 5 years, there will be studies that intensify therapy with novel agents in patients with high-risk disease—for example, those who have a PET2 positivity, versus minimizing therapy and substituting novel agents rather than radiation or more toxic chemotherapies in patients with very good prognoses.

This is a very fertile field, and it’s continuing to evolve. But, I think there’s a clear direction that needs to be evaluated for these patients.

This year’s ASH Annual Meeting included a variety of trials in Hodgkin lymphoma. They were clinically meaningful. Several of these included the plenary presentation that looked at ECHELON-1 and, certainly, the incorporation of novel therapies in this population.

Given the role of novel therapies, particularly checkpoint inhibitors, a variety of studies also looked at response assessment with this. I’d like to point to Dr. Cohen’s presentation from Emory. He presented treatment beyond progression with nivolumab in this population. This is an important study because it looked at patients with relapsed/refractory disease in cohorts A, B, and C in the CheckMate-205 study. It looked at patients who had progressed by criteria that have been well established and explored how they would respond to additional therapy. Those of us who treat Hodgkin lymphoma, that use checkpoint inhibitors, clearly see benefits—in patients who continue to have progression—by radiographic criteria. Determining how to evaluate patients who are clinically benefiting but are radiographically showing progression is an important clinical question.

So, this identified 70 such patients. Approximately half of them showed continued benefit with tumor reduction, despite being identified as having progression, radiographically. The important point is to note that not all progressions are the same. Judgment must be used in determining how to evaluate tumor progression in checkpoint inhibitor therapy, because assessment of PET scans is complicated by the immune response.

This study showed that if the patient is clinically benefiting and the progression is such that the patient could continue on therapy, there may be added value in continuing checkpoint inhibitor therapy in this population. For those of us who practice, that’s an important aspect to treatment of Hodgkin lymphoma. This is underappreciated in both the community and academic centers.

Transcript Edited for Clarify