TY - JOUR
T1 - Lenalidomide, bortezomib, and dexamethasone combination therapy in patients with newly diagnosed multiple myeloma
AU - Richardson, Paul G.
AU - Weller, Edie
AU - Lonial, Sagar
AU - Jakubowiak, Andrzej J.
AU - Jagannath, Sundar
AU - Raje, Noopur S.
AU - Avigan, David E.
AU - Xie, Wanling
AU - Ghobrial, Irene M.
AU - Schlossman, Robert L.
AU - Mazumder, Amitabha
AU - Munshi, Nikhil C.
AU - Vesole, David H.
AU - Joyce, Robin
AU - Kaufman, Jonathan L.
AU - Doss, Deborah
AU - Warren, Diane L.
AU - Lunde, Laura E.
AU - Kaster, Sarah
AU - DeLaney, Carol
AU - Hideshima, Teru
AU - Mitsiades, Constantine S.
AU - Knight, Robert
AU - Esseltine, Dixie Lee
AU - Anderson, Kenneth C.
PY - 2010/8/5
Y1 - 2010/8/5
N2 - 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/m2 (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/m2, 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.
AB - 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/m2 (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/m2, 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.
UR - https://www.scopus.com/pages/publications/77954618168
U2 - 10.1182/blood-2010-02-268862
DO - 10.1182/blood-2010-02-268862
M3 - Article
C2 - 20385792
AN - SCOPUS:77954618168
SN - 0006-4971
VL - 116
SP - 679
EP - 686
JO - Blood
JF - Blood
IS - 5
ER -