Lenalidomide and rituximab in Waldenstrom's macroglobulinemia.
OBJECTIVE
Thalidomide and its more potent immunomodulatory derivative lenalidomide enhance rituximab-mediated antibody-dependent cell-mediated cytotoxicity. We therefore evaluated lenalidomide and rituximab in symptomatic Waldenstrom's macroglobulinemia (WM) patients naive to either agent.


METHODS
Intended therapy consisted of 48 weeks of lenalidomide (25 mg/d for 3 weeks and then 1 week off) along with rituximab (375 mg/m(2)/wk) dosed on weeks 2 to 5 and 13 to 16. Sixteen patients were enrolled, 12 of whom were previously untreated.


RESULTS
Unexpectedly, we observed an acute decrease in hematocrit in 13 of 16 patients (median hematocrit decrease, 4.8%), which was attributable to lenalidomide patients and which led to cessation of further enrollment on this study. Lenalidomide-related anemia was observed even at doses as low as 5 mg/d and occurred in the absence of hemolysis or other cytopenias. The overall response and major response (<50% decrease in serum IgM) rates were 50% and 25%, respectively, on an intent-to-treat basis. With a median follow-up of 31.3 months, 4 of 8 responding patients have progressed with a median time to progression of 18.9 months.


CONCLUSIONS
Lenalidomide produces unexpected but clinically significant acute anemia in patients with WM. In comparison with our previous study with thalidomide and rituximab in an analogous patient population, the responses achieved in WM patients with lenalidomide and rituximab appear less favorable.
Treon
Steven P
SP
Bing Center for Waldenstrom's Macroglobulinemia, Dana-Farber Cancer Institute, Boston, MA 02115, USA. steven_treon@dfci.harvard.edu
Soumerai
Jacob D
JD
Branagan
Andrew R
AR
Hunter
Zachary R
ZR
Patterson
Christopher J
CJ
Ioakimidis
Leukothea
L
Chu
Luis
L
Musto
Paul
P
Baron
Ari D
AD
Nunnink
Johannes C
JC
Kash
Joseph J
JJ
Terjanian
Terenig O
TO
Hyman
Paul M
PM
Nawfel
Elena L
EL
Sharon
David J
DJ
Munshi
Nikhil C
NC
Anderson
Kenneth C
KC
D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000139:chemically induced*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D058846:Antibodies, Monoclonal, Murine-Derived; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007075:Immunoglobulin M / Q000097:blood; D000077269:Lenalidomide; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D000069283:Rituximab; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D013921:Thrombocytopenia / Q000139:chemically induced; D008258:Waldenstrom Macroglobulinemia / Q000188:drug therapy*
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D007075:Immunoglobulin M; D000069283:Rituximab; D013792:Thalidomide; D000077269:Lenalidomide