The role of interferon-alfa (Intron A, Roferon) in the management of patients with low-grade NHL remains controversial. More than 10 randomized trials have been reported.\n\nA recent meta-analysis concluded that interferon appeared to afford a benefit with regard to progression-free and overall survival, but only when it was used in combination with aggressive chemotherapy (Rohatiner et al: Proc Am Soc Clin Oncol 17:4a[abstract 11], 1998). However, this meta-analysis did not include a large negative Southwest Oncology Group (SWOG) trial (Dana et al: Proc Am Soc Clin Oncol 17:3a[abstract 10], 1998).\n\nOne of the most notable interferon trials, conducted by the GELA group (Solal-CÃ©ligny et al: J Clin Oncol 16:2332-2338, 1998), led to the FDA approval of interferon in combination with an anthracycline regimen for indolent NHL. Coiffier and coworkers conducted a subsequent trial based on these data, which was presented at the ASH meeting (abstract #2003). Elderly patients with low-grade NHL were randomized to CHVP (cyclophosphamide, doxurubicin, VP-26, and prednisone) plus interferon or fludarabine. The response rate, time to progression, and survival favored the multiagent arm. However, as noted above, there are now fludarabine-based combinations that appear to be more effective than the single agent, and one of these would be a reasonable arm for a similar comparative trial. Moreover, recent enthusiasm for new monoclonal antibodies will likely replace interest in the interferon-based regimens.