Fifteen-year follow up reveals cure potential in follicular lymphoma

Unlike some other forms of lymphoma, advanced stage follicular lymphoma is considered incurable. But a new analysis of long-term data on patients treated for the disease years ago with standard regimens of immunotherapy and a chemotherapy combination known as CHOP suggests that many of those patients can now be considered cured.

The analysis is just published in the journal JAMA Oncology. 

A subset of advanced-stage follicular lymphoma patients can achieve cure with CHOP-based chemoimmunotherapy, as relapse rates decline over time. 

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."

Jonathan W. Friedberg, MD, MMSc, Wilmot Cancer Institute Director, University of Rochester Medical Center, senior and corresponding author on the paper

Historically, follicular lymphoma has been considered an incurable disease, with most patients experiencing relapses even years after initial treatment.

The JAMA Oncology paper reports on an analysis of follow-up data from patients with advanced follicular lymphoma who had been treated with a standard first-line chemoimmunotherapy regimen on a large clinical trial.

Roughly 70 percent of the patients remained alive 15 years after beginning treatment, and a statistical method known as cure modeling estimated that 42 percent of treated patients had been cured.

Cure modeling incorporates background mortality rates in an analysis of patient survival data to estimate what fraction of a group of patients can be considered cured of a disease. Such modeling accounts for the fact that over time some patient deaths will occur that are unrelated to the given disease.

The researchers applied a cure model to 15-year follow-up data from the S0016 clinical trial (NCT00006721) conducted by the SWOG Cancer Research Network, a clinical trials group funded by the National Cancer Institute (NCI), part of the National Institutes of Health (NIH), with the participation of other groups within the NCI-funded National Clinical Trials Network (NCTN).

This phase 3 trial, which opened in 2001, enrolled patients with untreated advanced-stage CD20-positive follicular lymphoma and randomized 531 of them to one of two treatments, both of which were built around a core chemotherapy regimen known as CHOP (cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone). One arm treated patients with rituximab plus the CHOP combination (R-CHOP), while the other arm used CHOP followed by radioimmunotherapy (CHOP-RIT). Primary results of the S0016 trial were published in 2013 (Press, OW. J Clin Oncol. 2013).

The S0016 modeling, including cure analysis, was carried out by Michael LeBlanc, PhD, a biostatistician at Fred Hutch Cancer Center and director of SWOG's Statistics and Data Management Center (SDMC), and Hongli Li, MS, also at the Hutch and the SWOG SDMC. 

It showed that, with a median follow-up time of 15.5 years after a patient had begun treatment, the rate of disease relapse dropped substantially over time, falling from 6.8 percent of patients relapsing in the first 5 years to only 0.6 percent relapsing between years 15 and 20.

Fifteen years after starting treatment, about 70 percent of patients remained alive. The analysis also showed no statistically significant difference between the two treatment arms in the rates of 15-year overall survival.

Based on their work, the authors conclude that a substantial subset of patients with advanced-stage follicular lymphoma can, when treated with a standard regimen that includes immunotherapy and chemotherapy, achieve a functional cure – defined as having no chance of lymphoma recurring during the patient's expected lifespan.

"These results reinforce that front-line chemoimmunotherapy remains an important option-particularly for appropriate patients-because it can deliver long-term disease control after a time-limited course of treatment, " said Mazyar Shadman, MD, MPH, of Fred Hutch Cancer Center, who is first author on the paper. Shadman is medical director of cellular immunotherapy at Fred Hutch, where he holds the Innovators Network Endowed Chair.

"As we bring novel agents into the first-line setting, the durability seen here sets a high benchmark; new strategies should aim not only to improve short-term response rates but to match or exceed long-term remission and cure potential."

The idea that many of these patients can be cured could change how newly diagnosed patients are counseled and could eliminate the need for indefinite oncology and radiologic follow-up visits after treatment, with patients eventually transitioning from oncology care back to a primary care team.

This study was supported by the NIH/NCI through grants U10CA180888 and U10CA180819.

Additional authors on the paper include Lisa Rimsza, MD, University of Arizona; John P. Leonard, MD, New York University; and Sonali M. Smith, MD, University of Chicago Medicine.