Five studies found treatment improvements in stage IV follicular lymphoma patients

Notable survival improvements have occurred with the incorporation of interferon alfa in 1982 and the introduction of rituximab in 1997.

Issue: May 1, 2006

Developing therapies, including the introduction of biologic agents and effective salvage methods, have led to significant outcome improvements for patients with stage IV follicular lymphoma, according to researchers from the University of Texas MD Anderson Cancer Center in Houston.

“Our data indicate a more pronounced improvement in overall survival than failure-free survival,” said Qi Liu, MD, from the department of lymphoma/myeloma at MD Anderson. “We analyzed the survival after first relapse, and observed that there has also been a steady improvement in survival after first relapse over the years.

Better salvage therapy

“Therefore, the progress in survival is probably due, at least in part, to improvements in salvage therapies,” Liu wrote in the Journal of Clinical Oncology.

An unexpected finding was the trend toward a plateau in the failure-free survival curve, initiated about eight to 10 years from the start of treatment.

Five consecutive trials

Many experts consider advanced-stage follicular lymphoma to be incurable. Currently, clinicians manage stage IV disease according to the following protocols: observation without therapy, regimens based with alkylating agents, fludarabine (Fludara, Berlex)-based treatment, dose intensification with transplantations, biologic therapies and treatment that targets the CD20 antigen.

To assess the patterns of outcomes for patients with advanced-stage follicular lymphoma, Liu and colleagues analyzed five consecutive studies involving 580 patients. They looked for patterns of overall survival, failure-free survival and survival after first relapse. All studies had been conducted at MD Anderson.

In the five study cohorts, patients received the following respective regimens: cyclophosphamide, doxorubicin, vincristine, prednisone and bleomycin (CHOP-Bleo); CHOP-Bleo followed by interferon alfa; a rotation of three regimens (alternating triple therapy), followed by interferon alfa; fludarabine, mitoxantrone (Novantrone; Immunex, Wyeth-Ayerst) and dexamethasone (FND) followed by interferon alfa; and FND plus delayed vs. concurrent rituximab (Rituxan; Genentech, Biogen Idec) followed by interferon alfa.

Researchers followed patients for up to 25 years. They used the follicular lymphoma international prognostic index (FLIPI) to critically assess for heterogeneity of clinical features among cohorts.

Stepwise improvements

From cohort 1 to cohort 5, there were improvements in overall survival (from 64% to 95%) and failure-free survival (29% to 60%). They noted a surprising trend toward a plateau in failure-free survival after about eight to 10 years.

For all 580 patients, the median survival was 12.7 years. To date the median survival times for patients on the two most recent studies (cohorts 4 and 5) have not been reached, Liu said.

Researchers obtained five-year survival data for all five study cohorts. Notable survival increments occurred with the incorporation of interferon alfa in 1982 and with the introduction of rituximab in 1997.

There were also consecutive improvements in failure-free survival. At 15 years, 13% of patients in cohort 1 remained disease-free, compared with 24% of patients in cohort 2 and 32% of patients in cohort 3. The overall failure-free survival curve appeared to plateau after eight to 10 years. The researchers supposed this leveling off might reveal a possible cure for some patients.

The median failure-free survival for all patients was 4.3 years (2.8 years in cohort 1 and 4.8 years in cohort 4).

Liu and colleagues noted factors that affected survival: Age older than 60, an elevated lactate dehydrogenase level and involvement of more than four nodal sites all led to a significant decline in overall and failure-free survival (P<.01 for all variables). Although a hemoglobin level of less than 12 g was associated with a significant decrease in inferior failure-free survival (P=.05), it did not adversely affect overall survival, according to the study.

A FLIPI score of 3 or greater had a highly significant adverse effect on both overall and failure-free survival compared with a FLIPI score of 1 or 2 (P<.001). – by Rebekah Cintolo

For more information:

Liu Q, Fayad L, Cabanillas F, et al. Improvement of overall and failure-free survival in stage IV follicular lymphoma: 25 years of treatment experience at The University of Texas M.D. Anderson Cancer Center. J Clin Oncol. 2006;24:1582-1589.