This year’s ASH Education Program features a look at the progress that has been made in the two centuries since Thomas Hodgkin entered medicine. Here, session chair Ann LaCasce, MD, previews the discussion, including novel therapeutic approaches and their economic impact.
It’s been nearly 200 years since Hodgkin lymphoma was recognized. How will you and the speakers mark this milestone?
This session will acknowledge the progress that has been made in treating the disease – particularly the amazing advances we’ve seen in just the past decade. These advances are driven by better understanding of the biology, such as how the regulation of 9p24.1 results in high expression of PDL1 and PDL2 and makes Hodgkin lymphoma uniquely sensitive to checkpoint inhibitors.
Since its approval several years ago, brentuximab vedotin, a CD30-targeting antibody drug conjugate, has also moved the field forward. We now have several other novel oral drugs that target certain pathways within the Reed-Sternberg cells and investigational approaches focusing on the immune microenvironment. There are also some new approaches using CD30-targeting chimeric antigen receptor (CAR) T cell therapies and cytotoxic T cells directed at Epstein-Barr virus.
Andrew Evans, MD, a leader in clinical trials in this disease, will discuss the management of geriatric patients – what we know about treatment options, ongoing trials, and balancing efficacy and toxicity. This is an especially challenging population because older patients typically cannot tolerate our standard therapies well, often present with more advanced disease, and have worse outcomes independent of treatment. We still have a long way to go in this area.
Scott Huntington, MD, MPH, will cover drug pricing and cost-effectiveness of therapies for newly diagnosed Hodgkin lymphoma, including the financial and societal implications of treatment. For example, a recent study showed that patients had improved modified progression-free survival with brentuximab plus AVD chemotherapy (doxorubicin, vinblastine, dacarbazine), compared with standard ABVD chemotherapy (doxorubicin, bleomycin, vinblastine, dacarbazine). So, patients do well when brentuximab vedotin is added AVD, but can we improve outcomes without adding such an expensive drug to the regimen? Is there a way to select which patients get that drug? How do the costs of therapy influence our answer to that question? Incorporating cost-effectiveness should bring an interesting and nuanced view to the overall topic.
What does the future of Hodgkin lymphoma research and drug development hold? What directions are researchers exploring?
Moving forward, our challenge will be combining and sequencing therapies to maximize disease control and minimize the therapy’s side effect profiles. Radiation, for example, can have significant long-term effects on a typically younger patient population who are in the prime of their lives. In addition, as the U.S. population ages, we see more geriatric patients with Hodgkin lymphoma. How can we best manage these patients: Is it checkpoint inhibitors or novel agents? How do we cause less toxicity at both ends of the age spectrum that we see with this disease?
As patients are receiving active agents such as brentuximab or nivolumab upfront, fewer will need additional therapies down the line because there will be presumably lower rates of recurrence. Then, the question becomes, “How do we approach patients with relapsed and refractory disease who have already had checkpoint inhibitors and brentuximab?” That may be where we can use CAR T cells, other immunotherapy approaches, or novel targeted agents and combinations.
What will attendees take away from this session?
First, a sense of increasing optimism. Those of us who treat Hodgkin lymphoma love treating it because patients generally do well. Even for patients who develop relapsed or refractory disease, we have good options. Dr. Huntington will leave us with a lot to consider regarding how we approach implementing results from clinical trials into standard practice. Once we have a positive trial, does that always mean that a new agent should become the standard of care, regardless of price?