By Shira Klapper, Senior Writer/Editor

A new study strikes an encouraging note for patients with diffuse large B-cell lymphoma (DLBCL) who remain in remission two years from their initial diagnoses. According to a Journal of Clinical Oncology (JCO) study published online ahead of print (February 18, 2014), patients who reach the 24-month mark without relapsing have an overall survival rate similar to people in the general population.

	Matthew J. Maurer, MS

“In other words, if you achieve event-free survival [EFS] at 24 months, the overall likelihood of survival in the next five years is now essentially the same as it was prior to your diagnosis,” said Matthew Maurer, MS, first author of the study, “Event-free Survival at 24 Months Is a Robust Endpoint for Disease Related Outcome in Diffuse Large B-cell Lymphoma Treated with Immunochemotherapy.” Event-free survival is defined as the absence of death, recurrence, or retreatment after a patient’s initial therapy.

Immunochemotherapy, which combines the monoclonal antibody rituximab with anthracycline-based chemotherapy, improved outcomes in the treatment of DLBCL when it was introduced in the early-2000s. The combination chemotherapy, commonly given as the regimen “R-CHOP,” delivers strong results, with most patients achieving cure or remission. However, doctors noticed—and studies have since shown—that patients on R-CHOP quickly separate out into two groups.

 “There’s a dichotomy of patients who do really well versus patients for whom the initial therapy is not enough,” said Mr. Maurer, a biostatistician at the Mayo Clinic in Rochester, Minnesota. “Nearly a third of patients will either not respond well to initial therapy or respond but relapse early—most commonly within the first year or two—and they generally have a poor outcome. But for those who survive two years without an event, the risk of relapse drops dramatically,” so much so, that only 3.6% of DLBCL patients will have a relapse five years or later after their initial diagnosis, according to a 2010 study in JCO.

Maurer and his colleagues considered this survival data in light of the fact that the median age of a patient with DLBCL in their registry is 63. Could it be, they wondered, that the risk of relapse after 24 months is low enough that it poses no more of a mortality risk than heart disease, diabetes, and other diseases that tend to accumulate as people grow into their 60s?

To answer this question, the research team looked at data from patients prospectively enrolled in the University of Iowa/Mayo Clinic Specialized Programs of Research Excellence (SPORE) Molecular Epidemiology Research and a North Central Cancer Treatment Group (NCCTG) clinical trial from 2002-2009. To increase the validity of their results, the researchers replicated their findings using data from patients treated on Groupe d'Etude des Lymphomes de l'Adulte (GELA) clinical trials and a set of patients from Lyon, France.

Their findings: When compared with people of the same sex and age, patients with DLBCL who survived event-free for two years had the same overall survival as the general population.

“While this doesn’t mean cure, doctors can reassure patients who achieve EFS at 24 months that their overall likelihood of surviving the next five years is now essentially the same as it was prior to their diagnosis.”

Maurer and his team also assessed whether clinical trials of DLBCL could effectively end at the 24 month mark rather than the traditional endpoint of continuous event-free survival over time. 

“We simulated clinical trials to assess drug-improving outcomes,” said Mr. Maurer. “And I compared what the power would be to detect differences, either using continuous EFS as is traditionally done or the EFS24 endpoint.”

“What came out of this is that EFS24 is a pretty good endpoint. It might allow us to use earlier endpoints for clinical trials, making the clinical research process quicker and more efficient.”

And that’s news doctors can take to the clinic.

Matthew J. Maurer, MS, is an Assistant Professor of Biostatistics in the Department of Health Sciences Research at the Mayo Clinic, Rochester. He is part of the research team for Lymphoma Molecular and Epidemiology Research, a large cohort study of over 6,000 newly diagnosed lymphoma patients enrolled at the Mayo Clinic and the University of Iowa. He is also a member of the biostatistics cores of the University of Iowa/Mayo Clinic Lymphoma SPORE and Mayo Clinic Ovarian SPORE. 

Source

Click here to read the abstract.
 

Click here to view a PDF of the full article.

Maurer, MJ, Ghesquières H, Jais J, et al. Event-free survival at 24 months is a robust endpoint for disease related outcome in diffuse large B-cell lymphoma treated with immunochemotherapy. J Clin Oncol. 2014; Published online ahead of print 2.18.2014.
 

The Exclusive Coverage series on ASCO.org highlights selected research from JCO with additional perspective provided by the lead or corresponding author.

@ 2014 American Society of Clinical Oncology