Importance of Individualized Therapy, Prognostication, and Prediction in the Treatment of Hodgkin Lymphoma

At the 2024 Great Debates and Updates (GDU) in Hematological Malignancies in New York City, New York, Andrew Evens, DO, MBA, MSc, Rutgers Cancer Institute of New Jersey, discusses the importance of individualized therapy, prognostication, and prediction in the treatment of Hodgkin lymphoma (HL).

Transcript:

Hi, my name is Dr. Andy Evans. I am at the Rutgers Cancer Institute of New Jersey. I'm the Deputy Director for Clinical Services and Medical Director for the RWJBarnabas Health Oncology Service Line.

I was happy to speak at today's conference on the topic of Hodgkin Lymphoma, including prognostication, prediction, and trying to engender individualized therapy. We've known now for years, if not decades, that Hodgkin lymphoma is curable.

When we say curable, that means at 2, 3, 5 years there's remission that's long lasting. That's important, but of course there's different stages and different unique patient characteristics. I spoke a little bit about prognostication, and I talked about it in the big picture [that] we have prognostic models based on pretreatment characteristics, such as age, certain blood counts, and [disease] stage.

I think these models are good, but where we have opportunities to improve is [asking], “Are they prognostic or predictive?” Those are 2 different things. When we say prognostic, it's associated with outcome, but does it change our therapy or help our decision making? I think [that] not just [with] Hodgkin lymphoma, but all lymphoma [and] maybe all cancer, is just dig a little deeper [to] get a little more granular.

[In] a lot of our models in lymphoma, we use a lot of dichotomization. I would argue we're addicted to dichotomization. In other words, over age 60, less than age 60. We know patients are different, whether they're 20, 35, 59, [or] 65.

We have a global consortium called Holistic Hodgkin Lymphoma International Study for Individual Care that started in 2018. The goal of that was to harmonize the world's data in Hodgkin Lymphoma, all stages [from] early stage [to] advanced stage.

To do this (not just for clinical trials, [which are] pivotal phase 3 randomized clinical trials, whether RATHL, RAPID and others that give us that initial acute follow-up within 3 to 5 years), we've also included international and, in some cases, national prospective cancer registries that will follow patients for 10, 20, 30 years working with BC Cancer in Vancouver, Stanford, Princess Margaret, Australia, Iowa Mayo Spore and others, because we want to get that late effect.

Great [that] we're curing patients, but most patients with Hodgkin lymphoma are younger [in their] 20s and 30s, so of course we want to cure, but concurrently do no harm. When I say do no harm, [it’s] not during treatment, but through the first 10 years after treatment and beyond. We've leveraged now close to 20,000 individual patient cases with rigorous modeling, not just prognostication, but predictive modeling, where we do detailed statistical analysis, not just discrimination but calibration. It's just the beginning where we were able to publish in [the Journal of Clinical Oncology] a new predictive model for advanced stage. But we want to look at early stage, relapsed/refractory, different treatments, and can we start to get to a point where we actually have objective data at not just a 3- and 5-year mark, but decades down the road, [or] before a patient starts treatment to help inform decision-making, that [is] based on their particular type of lymphoma, their characteristics, maybe even their family history. That [isn’t to] say, "This is the only treatment," but if you treat with A, B, C, or D, here are the expected outcomes at five years, and down the road. We're really excited about that work through Holistic [Hodgkin Lymphoma].

In terms of actual clinical trials, we highlighted an open national clinical trial in early-stage Hodgkin Lymphoma called AHOD2131. That's a study being led by the Children's Oncology Group, but all the adult lymphoma groups are collaborating and participating. It’s [including] ages 5 through 60 years old [and] are accruing. All early-stage patients, stage[s] 1 and 2, regardless of risk, are included. All patients receive 2 cycles of [doxorubicin, bleomycin, vinblastine, dacarbazine] (ABVD). The standard of care in most practices is continuing chemotherapy, maybe adding radiation. But in this study, it's going to be a pivot, randomization, to novel targeted therapeutic agents, in particular brentuximab vedotin and nivolumab checkpoint inhibitor therapy. That just opened a few months ago, so everyone should go to their local Cancer Trials Support Unit [CTSU] and really look at this study, AHOD2131.

We also talked about Hodgkin Lymphoma for advanced stages, where novel targeted therapeutics have already made more of a stamp in that field. We know with ECHELON-1, incorporating brentuximab vedotin with AVD, was really a landmark randomized clinical trial that [not only] showed improved progression-free survival, but was the first regimen to show an overall survival advantage versus classic ABVD. And that has never been shown in the field, and really was an important advance in our field to understand that. So that's great, but as always, we're never satisfied.

We also showed data showing the new clinical trial that was presented at last [American Society of Clinical Oncology] (ASCO)'s Plenary Session by Alex Herrera, [SWOG] S1826. That was comparing what we called the standard arm of ECHELON-1 to nivolumab AVD.

At least at 1 year at this plenary session, it showed an improved progression-free survival and looked to be better [globally] tolerated as well amongst all patients. I also highlighted a presentation by Dr. Sarah Rutherford at [the American Society of Hematology] ASH [meeting] as an oral presentation only in older patients. We need to understand why that improvement was even larger with nivolumab AVD versus brentuximab vedotin AVD.

But that was at 1 year, so of course I highlighted the importance [that] we need longer follow- up in terms of efficacy [and] tolerability. We hope this calendar year we'll see some more mature data on that important clinical trial.

Source:

Evens A. Reevaluating frontline therapy and beyond for hodgkin lymphoma: Strategies for optimal clinical decision-making and targeted therapy across patient groups. Presented at the 2024 Great Debates & Updates in Hematological Malignancies: April 5-6, 2024. New York City, NY.