Reviewer: John P. Plastaras, MD, PhD
Abramson Cancer Center of the University of Pennsylvania
Ultima Vez Modificado: 21 de marzo del 2007
Presenter: Pavlovsky, M A
Presenter's Affiliation: FUNDALEU, Argentina
Type of Session: Scientific
Chronic lymphocytic leukemia (CLL) is an indolent neoplasm of B-cell origin, that is usually CD20+, CD5+, and CD23+. It is similar to small lymphocytic lymphoma (SLL) where the disease burden is predominantly in lymph nodes and the bone marrow is minimally involved.
Fludarabine is the most active single agent in CLL. Rituximab is an anti-CD20 antibody that has complementary activity with fludarabine with minimal toxicity.
The combination of fludarabine, cyclophophamide, and rituximab (FCR) has demonstrated superior rates of complete remission (CR), minimal residual disease (MRD) negativity, disease-free survival (DFS) and overall survival (OS) in previously treated and untreated patients with CLL, when compared with historical control groups using fludarabine alone or fludarabine and cyclophosphamide.
CD28 is a marker of worse prognosis in CLL
This study was undertaken to evaluate the efficacy of FCR in improving CR, DFS and OS rates in patients previously treated with chlorambucil-prednisone and untreated patients with CLL.
Materials and Methods
Phase II single institution, single-arm, prospective study in patients with either untreated or previously treated with chlorambucil-prednisone eligible for symptomatic treatment.
41 patients completed treatment:
FCR induces a high CR and DFS rate and increases MRD negativity. Significantly higher DFS rates were observed in patients who were CD38 negative.
The combination regimen of fludarabine, cyclophosphamide, and rituximab in patients that were either treatment naïve or previously treated was associated with excellent remission rates. It was generally well-tolerated except for frequent neutropenic fever (33%).
This study confirms that previously treated patients have lower remission rates. Also, the cell surface marker, CD38 is a negative prognostic marker in CLL with this treatment regimen.
Rituximab has been a major addition to the armamentarium against B-cell diseases. It is particularly appealing for indolent B-cell NHL as it has minimal toxicity and can be combined fairly easily with other treatments. The ideal schedule of incorporation of rituximab is an active area of investigation in number B-cell histologies.