A phase 1/2 study of carfilzomib in combination with lenalidomide and low-dose dexamethasone as a frontline treatment for multiple myeloma

作者：Jakubowiak, Andrzej J.^*; Dytfeld, Dominik; Griffith, Kent A.; Lebovic, Daniel; Vesole, David H.; Jagannath, Sundar; Al-Zoubi, Ammar; Anderson, Tara; Nordgren, Brian; Detweiler-Short, Kristen; Stockerl-Goldstein, Keith; Ahmed, Asra; Jobkar, Terri; Durecki, Diane E.; McDonnell, Kathryn; Mietzel, Melissa; Couriel, Daniel; Kaminski, Mark; Vij, Ravi

来源：Blood, 2012, 120(9): 1801-1809.

DOI：10.1182/blood-2012-04-422683

• STEM-CELL TRANSPLANTATION
• THALIDOMIDE PLUS DEXAMETHASONE
• COMPLETE RESPONSE
• IRREVERSIBLE INHIBITOR
• INDUCTION TREATMENT
• ANTITUMOR-ACTIVITY
• BORTEZOMIB
• THERAPY
• SUPERIOR
• DOXORUBICIN

This phase 1/2 study in patients with newly diagnosed multiple myeloma (N = 53) assessed CRd-carfilzomib (20, 27, or 36 mg/m(2), 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/m(2)) 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. (Blood. 2012;120(9):1801-1809)

• 出版日期2012-8-30