Experts Debate the Role of Maintenance Rituximab in Follicular Lymphoma

October 2014, Vol 5 , No 8

New York, NY—In a debate on the role of rituximab (Rituxan) maintenance therapy in patients with follicular lymphoma at the 2014 National Comprehensive Cancer Network Congress, the protagonist and antagonist were not that far apart.

Taking the position of protagonist, Richard I. Fisher, MD, Cancer Center Director, Fox Chase Cancer Center, Philadelphia, PA, stated that maintenance therapy is indicated in all patients who are sensitive to rituximab.

Taking the side of antagonist in the debate, Andrew D. Zelenetz, MD, PhD, Vice Chair, Medical Informatics, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, said that he considers maintenance an option, but that it is not mandatory.

Two separate studies by the Swiss Group for Clinical Cancer Research showed that maintenance therapy with rituximab improved progression-free survival (PFS) compared with observation alone, and compared with short-term maintenance therapy, respectively, in patients who responded to initial rituximab. Neither trial showed an improvement in overall survival (OS) with maintenance therapy.

“These and other studies show that the use of maintenance therapy after chemotherapy prolongs the time patients are in remission,” Dr Fisher stated.

More recently, the PRIMA study looked at 1010 patients with follicular lymphoma and a high tumor burden who responded to R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy and were then randomized to maintenance therapy or to observation.

Rituximab maintenance was superior to observation at the planned interim analysis—the 2-year PFS rates were 82% versus 66%, respectively (P <.001). Maintenance therapy achieved superior PFS compared with observation in all subgroups. Maintenance therapy delayed time to the next antilymphoma treatment and to the next chemotherapy treatment.

Maintenance therapy has some risks, Dr Fisher noted, and probably should not be given longer than 2 years.

“The real question is not whether to give rituximab again, but whether to give it as maintenance or retreatment when patients relapse,” he stated. Studies to date suggest that either strategy will delay the time to chemotherapy, Dr Fisher added.

Remaining questions include the optimal duration of maintenance therapy, characterizing long-term complications, and whether newer agents will be an improvement over rituximab for maintenance therapy.

Other issues include the cost per life saved, and rituximab meets the current paradigm of <$100,000, Dr Fisher said. “This is cheaper than some targeted therapies,” he added.

“There are many questions, but you need to individualize the decision. A lymphoma expert should discuss maintenance therapy with a very well educated patient,” Dr Fisher concluded.

“My position is that maintenance therapy is not the standard of care. That doesn’t mean that it shouldn’t be used,” Dr Zelenetz told listeners. “My longest consultation is with a new patient with follicular lymphoma at diagnosis when we discuss treatment. My second longest consultation is whether the patient should get maintenance therapy or whether observation is a good option.”

Factors to consider include age, symptoms, short-term and long-term goals, and tumor characteristics.

“One of the big questions in follicular lymphoma is whether PFS should be the goal of treatment. Although OS is the preferred end point, it is a difficult end point in follicular lymphoma trials,” he noted.

“The conundrum is that OS improvements are unlikely in the absence of PFS, but PFS does not necessarily predict for OS in follicular lymphoma,” Dr Zelenetz explained.

“We would like to see a good relationship between OS and PFS. We see this in aggressive lymphoma, but not in follicular lymphoma. You can change PFS in a major way and not impact on OS,” he added.

Given the fact that maintenance therapy does not improve OS in any study to date, and that maintenance and retreatment at relapse have similar outcomes, Dr Zelenetz’s preferred strategy is the latter.

“The fact that maintenance rituximab gives you a durable benefit but no OS benefit makes the decision a discussion but not a requirement,” he stated.

“Living with the disease is like being in remission. These patients don’t have symptoms, but then they need retreatment. Clinical experience suggests that quality of life in remission is similar to that of low tumor burden. The major concern is risk of transformation,” Dr Zelenetz continued.

Patients may fall into 1 of 2 categories. The first is, “I can’t live with knowing I have active lymphoma.” They are the patients who get maintenance therapy (approximately 30% of Dr Zelenetz’s practice). The second group says, “I feel fine and don’t want treatment” (approximately 70% of his practice).

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