FDA Approval: Rituximab in Combination with Fludarabine and Cyclophosphamide for the Treatment of Patients with Chronic Lymphocytic Leukemia

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BlankFirst Published Online January 6, 2011

The Oncologist, doi: 10.1634/theoncologist.2010-0306

U.S. Food and Drug Administration Approval: Rituximab in Combination with

Fludarabine and Cyclophosphamide for the Treatment of Patients with Chronic

Lymphocytic Leukemia

J. Casaka, J. Lemerya, Yuan Li Shenb, Mark D. Rothmannb, Aakanksha

Khandelwalc, Hong Zhaoc, a, Vaishali Jarrala, Keegana,

Pazdura

aOffice of Oncology Drug Products, Office of New Drugs, bOffice of

Biostatistics, and cOffice of Clinical Pharmacology, Center for Drug Evaluation

and Research, U.S. Food and Drug Administration, Silver Spring, land, USA

Correspondence: Correspondence: J. Casak, M.D., Division of Biological

Oncology Products, U.S. Food and Drug Administration, 10903 New Hampshire

Avenue, Building 22, Room 5223, Silver Spring, land 20993, USA. Telephone:

301-796-2320; Fax: 301-796-9849; e-mail: .Casak@...

Received September 7, 2010; accepted for publication November 29, 2010.

Abstract

Purpose. To describe the clinical studies that led to the FDA approval of

rituximab in combination with fludarabine and cyclophosphamide (FC) for the

treatment of patients with chronic lymphocytic leukemia (CLL).

Materials and Methods. The results of two multinational, randomized trials in

CLL patients comparing rituximab combined with fludarabine and cyclophosphamide

versus FC were reviewed. The primary endpoint of both studies was

progression-free survival (PFS).

Results. The addition of rituximab to FC decreased the risk of a PFS event by

44% in 817 previously untreated patients and by 24% in 552 previously treated

patients. Median survival times could not be estimated. Exploratory analysis in

patients older than 70 suggested that there was no benefit to patients when

rituximab was added to FC. The safety profile observed in both trials was

consistent with the known toxicity profile of rituximab, FC, or CLL.

Conclusions. On the basis of the demonstration of clinically meaningful

prolongation of PFS, the FDA granted regular approval to rituximab in

combination with FC for the treatment of patients with CLL. The magnitude of the

treatment effect in patients 70 years and older is uncertain.