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F or the past 30 years, lymphoma experts have debated how to manage patients with indolent lymphoma who have a low tumor burden and no symptoms. Because most of them will need therapy eventually, should oncologists blast the disease with every regimen they can think of in a bid to cure or get it under control as soon as possible, even though there’s no evidence this improves survival? Or should they spare patients the toxic effects and simply observe the slow-growing disease until therapy is really needed? The debate reignites every time a promising new treatment emerges. It has become particularly vigorous over the last few years with the advent of biological therapies such as the monoclonal antibody rituximab (Rituxan), which provides longer-lasting remission with fewer side effects than chemotherapy. Data emerging in the last 3 years show that rituximab also improves survival in symptomatic follicular lymphoma—something that chemotherapy alone has not achieved. This finding has some holdouts wondering whether it might finally be time to abandon watch-and-wait for patients with less-threatening disease. The topic was the subject of a debate session at the meeting of the European Society of Medical Oncology in Berlin in late September 2009. Although watch and wait was a clear winner among the 200strong audience, with almost nobody raising a hand in favor of early treatment at the close, experts say the debate is very much alive in the wider field in both the United States and Europe. “When you have a disease where you can sit down and discuss with the patient, in the same conversation, anything from watch and wait to oral chemotherapy, intravenous chemotherapy with immunotherapy, radioimmunotherapy, and autologous bone marrow transplant, you know we don’t understand what the right answer is,” said Samuel Silver, M.D., Ph.D., a hematologist at the University of Michigan in Ann Arbor. About 40% of all non-Hodgkin lymphomas are indolent, with follicular lymphoma being by far the most common. Experts estimate that about one-third of those patients would be candidates for watch and wait because of a low tumor burden or absence of symptoms or other factors requiring immediate treatment. Most will eventually need treatment for this generally incurable disease, usually within 2–3 years, but a small proportion, perhaps 10%–20%, can go 10 years or more without therapy. The problem is that there’s no way to identify which patients can safely be spared unnecessary treatment. Until the late 1970s, immediate chemotherapy was standard, but thinking started to shift after a 1979 retrospective trial showed no difference in survival between immediate and delayed chemotherapy. Three randomized trials followed in the 1980s and 1990s, confirming no overall survival benefit from immediate chemotherapy, and from then on medical students and oncologists were taught that indolent lymphoma should be initially managed with watch and wait. “If you start treating immediately or delay it, the duration of life is the same. What changes is if you are in remission or not, but that doesn’t matter if you don’t have symptoms,” said Michele Ghielmini, M.D., head of oncology at the Oncology Institute of Southern Switzerland in Bellinzona. “So if you have a patient who has the disease but doesn’t notice he has it, why not let him live quietly until he has symptoms?”

Indolent Lymphoma: Can Rituximab Resolve the Watch-and-Wait Debate?