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.
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.
Zent
Clive S
CS
Division of Hematology, Mayo Clinic, Rochester, Minnesota 55905, USA. zent.clive@mayo.edu
LaPlant
Betsy R
BR
Johnston
Patrick B
PB
Call
Timothy G
TG
Habermann
Thomas M
TM
Micallef
Ivana N
IN
Witzig
Thomas E
TE
D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D000068338:Everolimus; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000473:pathology; D008198:Lymph Nodes / Q000473:pathology; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000627:therapeutic use
D000970:Antineoplastic Agents; D000068338:Everolimus; D020123:Sirolimus