Treatment Delay Feasible in Asymptomatic Follicular Lymphoma

Phoebe Starr

October 2011, Vol 2, No 6 - NCCN Hematology Congress


New York, NY—Evidence suggests that maintenance therapy, as well as initiation of therapy for newly diagnosed follicular lymphoma, can be delayed in asymptomatic patients with low tumor burden, according to Andrew Zelenetz, MD, Chief of Lymphoma Service, Memorial Sloan-Kettering Cancer Center, New York, NY.

Speaking at the National Comprehensive Cancer Network 6th Congress on Hematologic Malignancies, which he chaired, Dr Zelenetz said, “The quality of life for follicular lymphoma patients who are asymptomatic and living with their disease is similar to that of patients in remission.”

Although studies show that initial treatment and maintenance therapy improve progression-free survival (PFS) in patients with follicular lymphoma, no overall survival (OS) advantage has been reported.

The ability to delay therapy in this patient population has economic implications, because treatment with single-agent rituximab (Rituxan) costs approximately $36,000 annually per patient. Dr Zelenetz estimated that a treatment that costs this much but has no impact on OS would cost about “tens of millions of dollars” per quality-adjusted life-year, which is clearly unacceptable.

“Currently we have the luxury of using therapy that doesn’t impact OS, but I can’t predict the future. It might be difficult to get paid for maintenance rituximab,” he said.

Follicular lymphoma is an indolent B-cell lymphoma with a median survival of 12 to 16 years. Rituximab has dramatically improved PFS, but patients will eventually relapse. The decision to initiate therapy in an asymptomatic patient with follicular lymphoma rests on the patient’s preference. Dr Zelenetz said patients fall into 2 groups: those who want treatment for a disease they know they have, even if there are no symptoms, and those who are content to forego treatment while feeling well, preferring to receive treatment when they need it.

He cautioned against routine treatment for every newly diagnosed follicular lymphoma. Patients who require immediate up-front treatment are symptomatic and have a tumor >3 cm, cytopenia, concurrent disease transformation, or compromised end-organ function.

At least 4 different randomized clinical trials in patients with low tumor burden failed to show improvement in OS with any chemotherapy versus observation, suggesting that treatment can be delayed in these patients. Studies by the European Organization for Research and Treatment of Cancer and by the Swiss Group for Clinical Cancer Research, along with the PRIMA, RESORT, and FIT studies, have shown that several maintenance regimens, including radioimmunotherapy or rituximab dramatically improve PFS in follicular lymphoma, but none of these regimens improved OS. Dr Zelenetz noted that PFS is not an ideal end point and an OS benefit would be more convincing.

Researchers at Memorial Sloan- Kettering Cancer Center are studying disease proliferation as a marker for the timing of initial treatment of follicular lymphoma. Based on image analysis of MIB-1/Li-67 staining, the researchers determined that the median time to need for treatment was 5 years in patients with disease proliferation <30% versus 18 months in those with disease proliferation >30%.

They anticipate that markers such as disease proliferation will help ensure that available treatments are used more efficiently.