Rituximab as a Single Agent in Early CLL

[Guest guest]

ASH:

[1533] Single Agent Rituxan in Early Stage chronic

lymphocytic leukemia (CLL).

Deborah A. , O'Brien, Francis J. Giles,

Cortes, Stefan Faderl, Hagop Kantarjian,

Lerner, Razelle Kurzrock, Keating. Department

of Leukemia, M. D. Cancer Center, Houston,

TX; Department of Bioimmunotherapy, M. D.

Cancer Center, Houston, TX

Currently, patients with early stage CLL without

active disease are observed. However, those patients

with elevated beta-2 microglobulin levels appear to

have a shorter median survival (6 years versus 10+

years).

Strategies designed to impact the eventual progression

of disease include use of targeted therapies with

minimal long term risk. Single agent Rituxan has

activity in previously treated CLL [O'Brien S et al,

JCO 19:2165, 2001; Byrd J et al, JCO 19:2153, 2001],

and in untreated low grade lymphomas [Hainsworth D,

Sem Oncol 27:25, 2000].

We designed this study to investigate the activity of

Rituxan in untreated high risk, early stage CLL.

Patients were eligible if they had untreated Rai stage

0 to II CLL with beta-2 microglobulin levels 2.0

mg/dL, without indications for therapy according to

the NCI Working Group criteria. Rituxan was given 375

mg/m2 weekly for 8 weeks.

Baseline cytokine profiles known to be prognostic in

CLL, including IL-6, IL-10, and TNF-alpha [Fayad et

al, Blood 97:256, 2001], were obtained with serial

measurements when feasible.

Thirty-one patients have been enrolled to date;

characteristics were median age 67 years (range,

50-82), Rai stage II in 32%, and median beta-2

microglobulin 3.6.

The overall response rate in 21 evaluable patients [8

under active therapy, 2 not reassessed] was 90% (19%

complete response, 19% nodular PR, 48% PR).

Significant reductions in fatigue were reported. Two

patients did not respond.

With a median follow up of 8 months (range, 2-16), one

patient with PR progressed. No unexpected toxicities

were observed; most were grade I-II fever, chills,

and/or hypotension related to the first infusion.

Samples were collected for cytokine analysis in 10

patients to date. Although the numbers were small,

preliminary observations suggested reductions in

TNF-alpha levels correlated with response.

In conclusion, Rituxan has significant activity in

early stage CLL. Impact on survival and time to

progression requires longer follow up. Further

investigation of the effect of Rituxan on cytokine

profiles and implementation of strategies to modulate

CD20 expression is planned.

Keywords: chronic lymphocytic leukemia\ Rituximab\

Early stage

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