Single-agent rituximab in treatment-refractory or poor prognosis patients with chronic lymphocytic leukemia

Abstract

Objective:

Rituximab in combination with fludarabine and cyclophosphamide has significantly improved outcomes for patients with chronic lymphocytic leukemia (CLL) and an improvement in overall survival has recently been shown for the first time in the history of CLL treatment. However, the chemotherapy portion of this regimen may be unsuitable for elderly patients or those with significant comorbidities. We investigated the safety and tolerability of single-agent rituximab in 23 consecutive patients presenting with CLL at a single institution.

Research design and methods:

Patients received eight cycles of weekly rituximab (375 mg/m² initially). Patients progressing on rituximab treatment could receive up to five further courses of single-agent rituximab in escalating doses up to 3 gm/m² per dose. Previously untreated and previously treated patients, including those refractory to fludarabine, were eligible for the study.

Results:

Single-agent rituximab was efficacious, even in patients with treatment-refractory or poor-prognosis CLL. The overall response rate was 90.9% with a CR rate of 63.6%. The median PFS was 28.5 months, and median duration of response was 26 months. Responses were seen regardless of prior treatment including in patients refractory to fludarabine. Especially encouraging results were seen in patients receiving rituximab maintenance therapy who had a median duration of response substantially longer than those who did not receive maintenance (35 months vs. 14 months, respectively).

Conclusions:

Rituximab was well tolerated with no unexpected adverse events even at the highest dose. These results indicate that single-agent rituximab is effective and has a place in the treatment of CLL.

Key words::

• CLL
• fludarabine refractory
• Relapsed
• Rituximab monotherapy

Transparency

Declaration of funding

This work was partially supported by the Cancer Research Foundation, Chappaqua, NY, USA; and by F. Hoffmann La Roche Ltd, Nutley, NJ, USA.

Declaration of financial/other relationships

P.H.W. and G.U.A. have disclosed that they have no relevant financial relationships.

CMRO peer reviewers may have received honoraria for their review work. The peer reviewers on this manuscript have disclosed that they have no relevant financial relationships.

Acknowledgments

The authors would like to thank Rachel Edwards of Prism Ideas for providing writing assistance.

This article represents an update from a preliminary presentation given at the national meeting of the American Society of Hematology, New Orleans, LA, USA, December, 2009: Adiga GU, Wiernik PH. Single-Agent rituximab in treatment-refractory or poor prognosis patients with chronic lymphocytic leukemia. Blood (ASH Annual Meeting Abstracts), 2009;114:2380.