Blood cancers

Novel agents for follicular lymphoma: Who needs them?

The very good outcomes for most patients with follicular lymphoma leave only a small proportion who stand to benefit from novel treatments, an international expert has told the conference.

Professor Jonathan Friedberg, Director of the James P Wilmot Cancer Institute in Rochester, New York, told delegates follicular lymphoma is the second most common type of lymphoma, and the most common indolent form.

“Although it remains incurable, we have seen marked overall survival improvements in the past decade,” he said.

“Even among patients presenting with advanced stage follicular lymphoma, the median overall survival now exceeds 20 years. The majority of patients do very well with currently available therapies.”

In many cases patients die with, rather than from, the disease, as many are already aged in their 60s at the time of diagnosis.

Survival is now so good that conventional clinical trial measures such as progression-free survival are impractical for distinguishing between treatments.

“The continuing challenge, though, is to identify the subset of 20-30% of high-risk patients in whom the disease progresses after about two years, regardless of their treatment,” Professor Friedberg said.

“These patients are not easy to identify at diagnosis, and they are a key focus of research.”

Event-free survival two years after standard rituximab-containing chemo-immunotherapy, such as R-CHOP, has emerged as a powerful marker of sustained response. Among those patients, 10-year survival approaches 90% Professor Friedberg told delegates.

The search for biomarkers of a poor response, to identify patients who may benefit from novel therapies, has included analyses of immune-response 2 gene expression profiles, levels of cytokines such as IL-2, IL-1RA and CXCL9, and Bcl-2 mutations.

The well-established FL-IPI score has now been modified to include a panel of seven genes (the M7 FL-IPI score), providing an improved, but still imperfect, tool for identifying at-risk patients.

“We have also identified low serum vitamin D levels at diagnosis as a marker for inferior overall survival,” Professor Friedberg said.

“Vitamin D has a stronger association with survival than any of the FL-IPI risk factors, and is the first potentially modifiable risk factor. Unfortunately, we don’t yet know whether vitamin D levels are an independent risk marker, or just an indicator of more severe illness.”

A trial led by Professor Friedberg is currently exploring the addition of vitamin D to standard rituximab-based therapy.

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