Rituximab has been shown to prolong survival when used therapeutically with chemotherapy in Chronic Lymphocytic Leukemia(CLL). Rituximab, the mAb targeting CD20, was approved by the US FDA for patients with relapsed low-grade non-Hodgkin lymphoma. It is counterintuitive why Rituxan works in CLL. Relatively low levels of CD20 are expressed on CLL B cells, compared to normal B or neoplastic B cells of other lymphomas. In addition, soluble CD20 has been demonstrated in plasma of patients with CLL; this would be expected to “soal up” and inhibit the capacity of rituximab to bind to CLL B cells, thereby resulting in rapid clearance and negatively affecting pharmacokinetics. Standard-dose rituximab (375 mg/m2 weekly for 4 weeks) has very limited activity for patients with CLL. Dose-intense and dose-dense single-agent rituximab has been shown to increase efficacy but remains experimental. Rituxan at standard dose is listed by NCCN as a single agent only for frail patients who cannot tolerate other treatments. A 2005 guideline (Imre et al) says: “There is currently insufficient evidence to support or refute the additional use of rituximab as a maintenance therapy in patients who have completed chemotherapy plus rituximab.” However, NCCN doest list it as a single agent for the elderly. As recently as 2005, a recent guideline (Imre et al) said: “There is currently insufficient evidence to support or refute the additional use of rituximab as a maintenance therapy in patients who have completed chemotherapy plus rituximab.”
Since this guideline, additional evidence has accrued to support rituximab for maintenance in CLL. The strongest evidence in support of it was the Primary Rituximab and Maintenance (PRIMA) Study, in which patients received immunochemotherapy. Those who did not fail were randomly assigned to maintenance or observation. There was a longer progression-free survival in those who received rituximab maintenance, but no survival benefit. There also was a study, in which patients who could be observed were either randomly assigned to the watch-and-wait approach or to rituximab induction and maintenance. Time to requiring next treatment was longer if you got rituximab, but there was no survival benefit.
Not having a survival benefit means that the disease can be pushed off form coming back by using Rituxan but this treatment will not ultimately prolong life.
Currently(2012) are no guidelines that recommend maintenance rituximab.
The drugs thalidomide and lenalidomide, have also been investigated as maintenance treatment in CLL. Lenalidomide might have some validity as maintenance treatment and clinical trials of lenalidomide in maintenance treatment have been initiated.
Read the Professional version here.