Lenalidomide, bortezomib, and dexamethasone combination therapy in patients with newly diagnosed multiple myeloma.
This phase 1/2 study is the first prospective evaluation of lenalidomide-bortezomib-dexamethasone in front-line myeloma. Patients (N = 66) received 3-week cycles (n = 8) of bortezomib 1.0 or 1.3 mg/m(2) (days 1, 4, 8, 11), lenalidomide 15 to 25 mg (days 1-14), and dexamethasone 40 or 20 mg (days 1, 2, 4, 5, 8, 9, 11, 12). Responding patients proceeded to maintenance or transplantation. Phase 2 dosing was determined to be bortezomib 1.3 mg/m(2), lenalidomide 25 mg, and dexamethasone 20 mg. Most common toxicities included sensory neuropathy (80%) and fatigue (64%), with only 27%/2% and 32%/3% grade 2/3, respectively. In addition, 32% reported neuropathic pain (11%/3%, grade 2/3). Grade 3/4 hematologic toxicities included lymphopenia (14%), neutropenia (9%), and thrombocytopenia (6%). Thrombosis was rare (6% overall), and no treatment-related mortality was observed. Rate of partial response was 100% in both the phase 2 population and overall, with 74% and 67% each achieving very good partial response or better. Twenty-eight patients (42%) proceeded to undergo transplantation. With median follow-up of 21 months, estimated 18-month progression-free and overall survival for the combination treatment with/without transplantation were 75% and 97%, respectively. Lenalidomide-bortezomib-dexamethasone demonstrates favorable tolerability and is highly effective in the treatment of newly diagnosed myeloma. This study is registered at http://clinicaltrials.gov as NCT00378105.
Richardson
Paul G
PG
Dana-Farber Cancer Institute, Boston, MA 02115, USA. paul_richardson@dfci.harvard.edu
Weller
Edie
E
Lonial
Sagar
S
Jakubowiak
Andrzej J
AJ
Jagannath
Sundar
S
Raje
Noopur S
NS
Avigan
David E
DE
Xie
Wanling
W
Ghobrial
Irene M
IM
Schlossman
Robert L
RL
Mazumder
Amitabha
A
Munshi
Nikhil C
NC
Vesole
David H
DH
Joyce
Robin
R
Kaufman
Jonathan L
JL
Doss
Deborah
D
Warren
Diane L
DL
Lunde
Laura E
LE
Kaster
Sarah
S
Delaney
Carol
C
Hideshima
Teru
T
Mitsiades
Constantine S
CS
Knight
Robert
R
Esseltine
Dixie-Lee
DL
Anderson
Kenneth C
KC
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001897:Boronic Acids / Q000008:administration & dosage / Q000009:adverse effects; D000069286:Bortezomib; D003131:Combined Modality Therapy; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects; D005221:Fatigue / Q000139:chemically induced; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D000077269:Lenalidomide; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000601:surgery; D010146:Pain / Q000139:chemically induced; D011719:Pyrazines / Q000008:administration & dosage / Q000009:adverse effects; D012074:Remission Induction; D012678:Sensation Disorders / Q000139:chemically induced; D033581:Stem Cell Transplantation; D016019:Survival Analysis; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D016896:Treatment Outcome
D001897:Boronic Acids; D011719:Pyrazines; D013792:Thalidomide; D000069286:Bortezomib; D003907:Dexamethasone; D000077269:Lenalidomide
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