A randomized phase 2 study of lenalidomide therapy for patients with relapsed or relapsed and refractory multiple myeloma.
This multicenter, open-label, randomized phase 2 study evaluated 2 dose regimens of lenalidomide for relapsed, refractory myeloma. Seventy patients were randomized to receive either 30 mg once-daily or 15 mg twice-daily oral lenalidomide for 21 days of every 28-day cycle. Patients with progressive or stable disease after 2 cycles received dexamethasone. Analysis of the first 70 patients showed increased grade 3/4 myelo-suppression in patients receiving 15 mg twice daily (41% versus 13%, P = .03). An additional 32 patients received 30 mg once daily. Responses were evaluated according to European Group for Blood and Marrow Transplantation (EBMT) criteria. Overall response rate (complete, partial, or minor) to lenalidomide alone was 25% (24% for once-daily and 29% for twice-daily lenalidomide). Median overall survival in 30-mg once-daily and twice-daily groups was 28 and 27 months, respectively. Median progression-free survival was 7.7 months on once-daily versus 3.9 months on twice-daily lenalidomide (P = .2). Dexamethasone was added in 68 patients and 29% responded. Time to first occurrence of clinically significant grade 3/4 myelosuppression was shorter in the twice-daily group (1.8 vs 5.5 months, P = .05). Significant peripheral neuropathy and deep vein thrombosis each occurred in only 3%. Lenalidomide is active and well tolerated in relapsed, refractory myeloma, with the 30-mg once-daily regimen providing the basis for future studies as monotherapy and with dexamethasone.
Richardson
Paul G
PG
Dana-Farber Cancer Institute, 44 Binney St, Boston, MA 02115, USA. paul_richardson@dfci.harvard.edu
Blood
Emily
E
Mitsiades
Constantine S
CS
Jagannath
Sundar
S
Zeldenrust
Steven R
SR
Alsina
Melissa
M
Schlossman
Robert L
RL
Rajkumar
S Vincent
SV
Desikan
K Raman
KR
Hideshima
Teru
T
Munshi
Nikhil C
NC
Kelly-Colson
Kathleen
K
Doss
Deborah
D
McKenney
Mary L
ML
Gorelik
Svetlana
S
Warren
Diane
D
Freeman
Andrea
A
Rich
Rebecca
R
Wu
Anfang
A
Olesnyckyj
Marta
M
Wride
Kenton
K
Dalton
William S
WS
Zeldis
Jerome
J
Knight
Robert
R
Weller
Edie
E
Anderson
Kenneth C
KC
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use; D003907:Dexamethasone / Q000008:administration & dosage; D005260:Female; D006801:Humans; D000077269:Lenalidomide; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced; D012008:Recurrence; D012074:Remission Induction / Q000379:methods; D016879:Salvage Therapy / Q000009:adverse effects / Q000379:methods*; D016019:Survival Analysis; D015996:Survival Rate; D013792:Thalidomide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000633:toxicity; D020246:Venous Thrombosis / Q000139:chemically induced
D013792:Thalidomide; D003907:Dexamethasone; D000077269:Lenalidomide