The field of lymphoma research is experiencing big advances, as shown by sessions during the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting, held June 2-6 in Chicago and virtually. Patient Power spoke with Marc J. Braunstein, MD, PhD, assistant professor of medicine at NYU Long Island School of Medicine and Perlmutter Cancer Center, about his thoughts on how recent developments may affect patients, both in the short and long term.
“It's an exciting time to be in the field, and I think patients will certainly benefit now and down the road from various immunotherapy combinations,” Dr. Braunstein said. “We're well on our way to improving outcomes.”
Hodgkin Lymphoma: An Immunotherapy Study Produces Practice-Changing Data
At the ASCO Annual Meeting, the results of the SWOG S1826 trial were included in the plenary session, which highlights some of the most exciting research presented at the event. Nearly 1,000 patients with advanced-stage classical Hodgkin lymphoma enrolled in the trial, which compared two treatment regimens, both of which were combinations of immunotherapy and chemotherapy. One was the standard treatment, which is brentuximab with chemotherapy. The other was a new option, which is nivolumab plus chemotherapy.
Many people have described the results of the SWOG S1826 trial as “practice changing.” What did the study set out to learn, and what makes the results so strong?
Dr. Braunstein: We're making a lot of strides in lymphoma, particularly in Hodgkin lymphoma. Despite these excellent improvements in outcomes, there's still room for additional improvements in how we treat patients up front, particularly those who have an advanced need, which is typically stage III or IV, since these patients have a higher risk of relapsing.
Nivolumab is an immune checkpoint inhibitor, which reactivates immune cells called T-cells that are often shut down by tumor cells to avoid destruction by the patient's own immune system. These have revolutionized cancer care. Nivolumab is typically used in the relapse setting, but this study looked to see if it was superior to our current standard in the upfront setting with patients who have advanced classical Hodgkin lymphoma.
The study’s goal was to assess progression-free survival, which is a way of looking at how much time a patient is in remission until their cancer progresses. What this study showed is that progression-free survival was superior with nivolumab plus chemotherapy compared to the current standard of the brentuximab plus chemotherapy, with a one-year progression free survival of 94% versus 86%. I think this abstract is practice changing, because it shows an improvement in progression-free survival with nivolumab plus chemotherapy.
This study included patients aged 12 years to 86 years. How unusual is it to have a study with such a broad age range?
Dr. Braunstein: That is unusual. Usually, the adult research space and the pediatric space are separated. The median age for this study was 27 years, which is the typical age range of late adolescence/early adulthood, when we see Hodgkin lymphoma in the adult space. But about a quarter of the patients were younger than 18 years, which is unusual. To the authors’ credit, they enrolled a broad population to show that, regardless of age, this is an effective regimen.
What would it take for nivolumab plus chemotherapy to become the standard of care for newly diagnosed advanced-stage Hodgkin lymphoma?
Dr. Braunstein: One can argue that that this presentation alone is convincing enough to make nivolumab plus chemotherapy the new standard, but the data have not yet been published. So we want to see the full publication. It's always helpful to have the eventual maturation of the data and the follow-up showing the survival differences… But nonetheless, I think the study is very convincing and that the US Food and Drug Administration (FDA) should review the data and potentially approve nivolumab plus chemotherapy upfront for newly diagnosed advanced-stage Hodgkin lymphoma.
Refractory and Relapsed Follicular Cancer: Encouraging News About Bispecific Antibodies
Abstract 7506 reviewed data regarding the treatment of follicular lymphoma that has come back or that is not responding to treatment. In this study, under lead author Reid W. Merryman, MD, patients were treated with a bispecific antibody, called epcoritamab, combined with a standard second-line therapy that consisted of rituximab plus lenalidomide, called R-squared.
This study examined the use of epcoritamab, which is a bispecific antibody therapy. How do bispecific antibody therapies work?
Dr. Braunstein: We now have very sophisticated antibody therapies that don't just bind to one target on the surface of the lymphoma. Now we have bispecific antibodies that bind to two targets on the lymphoma cells. In doing so, they activate the T-cell, which is part of the immune system that can help destroy the lymphoma. It’s a relatively novel approach for how we treat various tumor types.
What types of patients were included in this study?
Dr. Braunstein: Patients with relapsed and refractory follicular lymphoma. This study was enhanced to include patients who have a more aggressive subtype of follicular lymphoma and didn't respond as well to their initial therapy as expected and who progressed from their first-line therapy within 24 months, which is typically associated with poor outcomes. About a third of patients in this study were in that higher-risk category.
What did this study set out to learn, and what were the outcomes?
Dr. Braunstein: This was a phase 1-2 study, which means they'd already established the safety evidence. With this study, they wanted to look into a larger population of patients in a nonrandomized way. In other words, everybody in the study got the treatment, and they wanted to see the early signs of efficacy.
The primary outcome of overall response was very impressive: 97%. That means that almost all patients in the study had some shrinkage of the lymphoma. That response generally correlates with progression-free survival and overall survival. They did look at the progression-free survival rate, and at six months it was 93%. Again, this study was enriched with patients who are at higher risk for progression, even within that six-month period. What was extremely impressive was when they looked at a subgroup of high-risk patients, the overall response rates were 95%.
I think the future of how we treat several different hematologic malignancies is using more immunotherapy and less chemotherapy. And that's certainly true based on based on this study.
When can we expect randomized data to confirm these results?
Dr. Braunstein: Probably about two to three years.
As treatments progress to include more immunotherapy and less chemotherapy, how may that benefit patients?
Dr. Braunstein: Conventional chemotherapy tends not to be specific, so there can be off-target effects, like hair loss, gastrointestinal side effects, and fatigue. Whereas targeted therapies like immunotherapies tend to have fewer off-target side effects that we generally associate with conventional chemotherapy. Not only are we improving outcomes, but we're also improving quality of life during the course of the treatment.
Were there any other studies presented at ASCO about lymphoma that might become practice changing?
Dr. Braunstein: Yes, there was a late-breaking abstract 107 by lead author Jason Westin, MD, which is an overall survival analysis of an earlier study called ZUMA-7 that was published last year.
It was a phase 3 randomized study of patients with aggressive diffuse large B-cell lymphoma who had not responded to their first-line therapy or relapsed within 12 months of their initial therapy. In other words, these patients were at higher risk for poor outcomes. They randomized patients to a CAR T-cell therapy versus the conventional standard, which is additional chemotherapy followed by an autologous stem cell transplant.
The initial publication in the New England Journal of Medicine last year showed that there was an improvement in event-free survival, which is like progression-free survival, in patients with the CAR T-cells, compared with the conventional standard of care. But we didn't have the overall survival benefit until this new landmark analysis was published. There was a significant improvement in overall survival at a median follow-up of 47 months. There's a 27% decrease in deaths with the CAR T-cells compared to the standard of care. Overall survival benefit is the gold standard outcome for a randomized study.
What was your overall impression of the lymphoma research presented at the ASCO conference? What does it say about the direction of this field?
Dr. Braunstein: This year's ASCO clearly shows we're making strides in various types of lymphoma: Hodgkin, non-Hodgkin, less aggressive, more aggressive. We're making better strides than we were with these new immunotherapy combinations.
Should patients discuss these studies with their oncologists to see if these results may affect their treatments?
Dr. Braunstein: It's always good to keep the lines of communication open with your oncologist. Not everything is necessarily applicable to each case, so it's always good to talk to your oncologist.
You can also speak about a clinical trial that might be available. Remember, all of the studies we've been discussing have been accomplished because patients have generously agreed to participate in clinical trials that – as we've seen – sometimes offer a superior therapy. It's important to talk to your oncologist if a clinical trial might be available and might be relevant at your phase of disease.