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Clinical Trial
. 2010 May 1;116(9):2201-7.
doi: 10.1002/cncr.25005.

The treatment of recurrent/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) with everolimus results in clinical responses and mobilization of CLL cells into the circulation

Clive S Zent  1 , Betsy R LaPlant, Patrick B Johnston, Timothy G Call, Thomas M Habermann, Ivana N Micallef, Thomas E Witzig
Affiliations
Clinical Trial

The treatment of recurrent/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) with everolimus results in clinical responses and mobilization of CLL cells into the circulation

Clive S Zent et al. Cancer. .

Abstract

Background: Patients with recurrent/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) often have chemotherapy-resistant disease, resulting in poor prognosis. The aim of this study was to learn if inhibition of the mammalian target of rapamycin (mTOR) would produce tumor responses.

Methods: This was a phase 2 study of oral single-agent everolimus (10 mg/day) for recurrent/refractory indolent lymphoid malignancies including CLL.

Results: Four of 22 patients with CLL (18%; 95% confidence interval, 5%-40%) achieved a partial remission to therapy. An unanticipated finding in this study was an increase in absolute lymphocyte count (ALC) associated with a decrease in lymphadenopathy in 8 (36%) patients. ALC increased a median of 4.8-fold (range, 1.9- to 25.1-fold), and the clinically measurable lymphadenopathy decreased a median of 75.5% (range, 38%-93%) compared with baseline measurements.

Conclusions: Everolimus has modest antitumor activity against CLL and can mobilize malignant cells from nodal masses into the peripheral circulation in a subset of CLL patients. Because CLL cells in lymphatic tissue and bone marrow can be more resistant to therapy than circulating CLL cells, the ability of everolimus to mobilize CLL cells into the circulation could be used in combination therapeutic regimens.

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Figures

Figure 1
Figure 1. Everolimus treatment resulted in an increase in the absolute lymphocyte count (ALC) and decrease in lymphadenopathy in 8 patients
The maximum decrease in the clinically measurable lymphadenopathy (node size) is shown by the grey bars) and associated increase in the ALC by the black bars.
Figure 2
Figure 2. Increase in the absolute lymphocyte count (ALC) from the pretreatment level to the time of maximum decrease in lymphadenopathy
See this image and copyright information in PMC

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