Follicular lymphoma, a common and usually slow-growing type of non-Hodgkin lymphoma (NHL), has long been deemed incurable: Though the disease responds well to initial treatment, oncologists tell patients to expect it to come back. New findings from a 15-year follow-up analysis of clinical trial patients with follicular lymphoma (FL) could upend that prediction, according to a study published today in JAMA Oncology.
Scientists at SWOG, Fred Hutch Cancer Center and the University of Rochester Medical Center looked at outcomes from FL patients who had received chemoimmunotherapy: a standard chemotherapy regimen (known as CHOP) plus an antibody-based immunotherapy (either CHOP plus rituximab or CHOP plus a radio-labelled antibody). Applying cure modeling to the 15 years-worth of follow-up data, the investigators showed a cure rate of 42% in the total population of trial participants.
The new findings could inform discussions with patients newly diagnosed with follicular lymphoma, said Fred Hutch lymphoma expert Mazyar Shadman, MD, MPH, who is the paper’s first author. Shadman directs the Bezos Family Immunotherapy Clinic and holds the Innovators Network Endowed Chair.
Currently, patients hear from their oncologists that folllicular lymphoma is incurable, but providers can send a different message now, Shadman said: “Follicular lymphoma could be curable, and it could be curable with standard chemo-immunotherapy.”
Follicular lymphoma is one of the most common types of NHL. About 15,000 people in the United States and Europe are diagnosed each year, and nearly 90% of them will survive at least five years past diagnosis. But according to current dogma, their cancer will return.
“This finding represents a paradigm shift in our understanding and approach to follicular lymphoma, with broad implications for initial patient discussions and future research strategies,” senior author and lymphoma expert Jonathan W. Friedberg, MD, MMSc, said in a SWOG press release. Friedberg directs the University of Rochester Medical Center’s Wilmot Cancer Institute.
Article continues below.
Learn more about our targeted approach to the diagnosis and treatment of non-Hodgkin (NHL) lymphoma.
The current work analyzed data from 532 patients who enrolled in a SWOG trial initiated in 2001 by the late Fred Hutch lymphoma physician-scientist Oliver Press, MD, PhD. Patients received CHOP, a combination of cyclophosphamide, doxorubicin, vincristine sulfate (Oncovin) and prednisone, plus an antibody-based immunotherapy (either rituximab or a radioactively labeled antibody). Fred Hutch and SWOG biostatisticians Michael LeBlanc, PhD, who directs SWOG’s Statistics and Data Management Center, and Hongli Li, MS, developed new methods to estimate how many patients were cured of their disease after 15 years.
The SWOG Cancer Network was one of the first cooperative groups created by the National Cancer Institute, and Shadman emphasized that the 15 years of follow-up, and the insights they enable, were only made possible by National Institutes of Health funding.
The team saw that relapse rates dropped over time, and 70% of patients (regardless of their regimen) were still alive 15 years after treatment. LeBlanc and Li’s cure calculations, which incorporate background mortality rates, suggest that after 15 years, 42% of patients were cured.
“We have always told patients that their follicular lymphoma will come back and we can’t cure them, mainly because we never had a 15-year follow-up of any studies,” Shadman said. “Now we’re showing that after a certain time, their chances of having progression of disease or dying from lymphoma are actually very similar to the general population.”
These findings could have long-reaching effects on patient care for people diagnosed with follicular lymphoma, Shadman said.
“We always start by saying ‘You start with me this year, you’ll stay with me for the rest of your life. We can treat your disease, but we'll never discharge you from the cancer center,’” he said. In contrast, some patients with other types of lymphomas (such as aggressive lymphomas) that are considered curable may eventually “graduate” back into a standard care environment.
“Now, we can just give the hope [to patients with follicular lymphoma] that yes, you may be someone who, after a few years, we can send back to your primary care provider,” Shadman said. “These findings also support eliminating the need for indefinite radiologic surveillance.”
The analysis also highlights how well R-CHOP (CHOP plus rituximab) can work, despite being a treatment regimen of long-standing. Oncologists could have a higher-level discussion with their patients, who Shadman said should not dismiss chemotherapy just because it’s chemotherapy and not the newest treatment available.
And if chemoimmunotherapy can cure some patients, the bar for new treatments has been set higher as well, Shadman noted. The analysis suggests that lower-risk FL patients were more likely to end up in that 42%, so it may also be that trials of new therapies should focus on patients with higher-risk FL who are less likely to be cured with standard treatment.
Shadman noted that the new work also highlights the importance of clinical trial participation. In addition to revealing the efficacy of a treatment, clinical trials also reveal potential long-term toxicities and side effects, such as risk of secondary malignancies.
“There is no way you can have a high-quality 15-year follow-up if patients are not in a clinical trial,” Shadman said.
The current analysis is the latest of multiple scientific papers to come out of the trial, initiated by Press, who mentored Shadman. Press was renowned for his mentorship, patient care and scientific vision.
He pioneered the development and use of radio-labeled antibodies, which help focus cancer-killing radiation in tumors, for lymphoma treatment. More than a decade later, the trial Press conducted is still providing insights that could improve patient care and future lymphoma research.
“It’s a wonderful testament to Ollie and his vision,” Shadman said.
Sabrina Richards, a senior editor and writer at Fred Hutch Cancer Center, has written about scientific research and the environment for The Scientist and OnEarth Magazine. She has a PhD in immunology from the University of Washington, an MA in journalism and an advanced certificate from the Science, Health and Environmental Reporting Program at New York University. Reach her at srichar2@fredhutch.org.
Are you interested in reprinting or republishing this story? Be our guest! We want to help connect people with the information they need. We just ask that you link back to the original article, preserve the author’s byline and refrain from making edits that alter the original context. Questions? Email us at communications@fredhutch.org
Every dollar counts. Please support lifesaving research today.
For the Media