High-dose chemotherapy, autologous stem cell transplantation failed to improve OS in follicular lymphoma

Al Khabori M. J Natl Cancer Inst. 2011;doi:10.1093/jnci/djr450.

Patients who underwent autologous stem cell transplantation for advanced follicular lymphoma did not experience an OS benefit, according to a systemic review and meta-analysis of trials involving 941 patients.

Al Khabori and colleagues said low-quality evidence suggests autologous stem cell transplantation (ASCT) was associated with improved event-free survival.

Results from seven trials were part of the systematic review, but only the four trials with data from 941 patients were included in this meta-analysis because outcome data were not available for pooling from three of the trials.

Patients were assigned to a variety of induction, mobilization and high-dose therapy regimens in the transplant and chemotherapy arms of the four trials. Patients received rituximab (Rituxan; Genentech, Idec Pharmaceuticals) in both arms during induction treatment in two of the trials.

Median follow-up was up to 5 years in two trials and roughly 9 years for the other two trials.

In the three trials that reported OS (n=701), researchers could find no statistically significant difference for patients who underwent high-dose chemotherapy (HDC) and ASCT compared with conventional-dose chemotherapy (pooled HR=0.99; 95% CI, 0.73-1.33). The quality of the evidence was rated as moderate.

All four trials included in the meta-analysis suggested an association between ASCT and improved event-free survival (pooled HR=0.54; 95% CI, 0.36-0.82) compared with high-dose chemotherapy. Researchers found that event-free survival was poorer in the trials that included rituximab as part of initial therapy (HR=0.38; 95% CI, 0.25-0.59) vs. those that did not (HR=0.60; 95% CI, 0.38-0.95).

Writing in an accompanying editorial, Caron A. Jacobson, MD, and Dan L. Longo, MD, of the department of medicine at Brigham and Women’s Hospital, said these results were timely in light of recent data on the efficacy of maintenance rituximab, which when added to various chemotherapeutic regimens has improved OS. Because the drug improves OS while maintaining a “modest” toxicity profile, it was the preferred treatment for a particular population of patients with advanced follicular lymphoma.

“We recommend rituximab maintenance therapy (in preference to HDC-ASCT) for patients achieving at least a partial response to first-line chemoimmunotherapy in the absence of any randomized controlled trials comparing the two,” they wrote. “HDC-ASCT is a powerful treatment strategy for patients with follicular lymphoma, but one that does not appear to be less effective in the setting of the first disease relapse than in primary treatment, and thus can be reserved for the salvage setting.”

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