TY - JOUR
T1 - A phase 1/2 study of carfilzomib in combination with lenalidomide and low-dose dexamethasone as a frontline treatment for multiple myeloma
AU - Jakubowiak, Andrzej J.
AU - Dytfeld, Dominik
AU - Griffith, Kent A.
AU - Lebovic, Daniel
AU - Vesole, David H.
AU - Jagannath, Sundar
AU - Al-Zoubi, Ammar
AU - Anderson, Tara
AU - Nordgren, Brian
AU - Detweiler-Short, Kristen
AU - Stockerl-Goldstein, Keith
AU - Ahmed, Asra
AU - Jobkar, Terri
AU - Durecki, Diane E.
AU - McDonnell, Kathryn
AU - Mietzel, Melissa
AU - Couriel, Daniel
AU - Kaminski, Mark
AU - Vij, Ravi
PY - 2012/8/30
Y1 - 2012/8/30
N2 - This phase 1/2 study in patients with newly diagnosed multiple myeloma (N = 53) assessed CRd - carfilzomib (20, 27, or 36 mg/m2, days 1, 2, 8, 9, 15, 16 and 1, 2, 15, 16 after cycle 8), lenalidomide (25 mg/d, days 1-21), and weekly dexamethasone (40/20 mg cycles 1-4/5+) - in 28-day cycles. After cycle 4, transplantation-eligible candidates underwent stem cell collection (SCC) then continued CRd with the option of transplantation. The maximum planned dose level (carfilzomib 36 mg/m2) was expanded in phase 2 (n = 36). Thirty-five patients underwent SCC, 7 proceeded to transplantation, and the remainder resumed CRd. Grade 3/4 toxicities included hypophosphatemia (25%), hyperglycemia (23%), anemia (21%), thrombocytopenia (17%), and neutropenia (17%); peripheral neuropathy was limited to grade 1/2 (23%). Most patients did not require dose modifications. After a median of 12 cycles (range, 1-25), 62% (N = 53) achieved at least near-complete response (CR) and 42% stringent CR. Responses were rapid and improved during treatment. In 36 patients completing 8 or more cycles, 78% reached at least near CR and 61% stringent CR. With median follow-up of 13 months (range, 4-25 months), 24-month progression-free survival estimate was 92%. CRd was well tolerated with exceptional response rates. This study is registered at http://www.clinicaltrials.gov as NCT01029054.
AB - This phase 1/2 study in patients with newly diagnosed multiple myeloma (N = 53) assessed CRd - carfilzomib (20, 27, or 36 mg/m2, days 1, 2, 8, 9, 15, 16 and 1, 2, 15, 16 after cycle 8), lenalidomide (25 mg/d, days 1-21), and weekly dexamethasone (40/20 mg cycles 1-4/5+) - in 28-day cycles. After cycle 4, transplantation-eligible candidates underwent stem cell collection (SCC) then continued CRd with the option of transplantation. The maximum planned dose level (carfilzomib 36 mg/m2) was expanded in phase 2 (n = 36). Thirty-five patients underwent SCC, 7 proceeded to transplantation, and the remainder resumed CRd. Grade 3/4 toxicities included hypophosphatemia (25%), hyperglycemia (23%), anemia (21%), thrombocytopenia (17%), and neutropenia (17%); peripheral neuropathy was limited to grade 1/2 (23%). Most patients did not require dose modifications. After a median of 12 cycles (range, 1-25), 62% (N = 53) achieved at least near-complete response (CR) and 42% stringent CR. Responses were rapid and improved during treatment. In 36 patients completing 8 or more cycles, 78% reached at least near CR and 61% stringent CR. With median follow-up of 13 months (range, 4-25 months), 24-month progression-free survival estimate was 92%. CRd was well tolerated with exceptional response rates. This study is registered at http://www.clinicaltrials.gov as NCT01029054.
UR - http://www.scopus.com/inward/record.url?scp=84865333050&partnerID=8YFLogxK
U2 - 10.1182/blood-2012-04-422683
DO - 10.1182/blood-2012-04-422683
M3 - Article
C2 - 22665938
AN - SCOPUS:84865333050
SN - 0006-4971
VL - 120
SP - 1801
EP - 1809
JO - Blood
JF - Blood
IS - 9
ER -