Lenalidomide and high-dose dexamethasone compared with dexamethasone as initial therapy for multiple myeloma: a randomized Southwest Oncology Group trial (S0232)

Abstract

The Southwest Oncology Group conducted a randomized trial comparing lenalidomide (LEN) plus dexamethasone (DEX; n = 97) to placebo (PLC) plus DEX (n = 95) in newly diagnosed myeloma. Three 35-day induction cycles applied DEX 40 mg/day on days 1 to 4, 9 to 12, and 17 to 20 together with LEN 25 mg/day for 28 days or PLC. Monthly maintenance used DEX 40 mg/day on days 1 to 4 and 15 to 18 along with LEN 25 mg/day for 21 days or PLC. Crossover from PLC-DEX to LEN-DEX was encouraged on progression. One-year progression-free survival, overall response rate, and very good partial response rate were superior with LEN-DEX (78% vs 52%, P = .002; 78% vs 48%, P < .001; 63% vs 16%, P < .001), whereas 1-year overall survival was similar (94% vs 88%; P = .25). Toxicities were more pronounced with LEN-DEX (neutropenia grade 3 or 4: 21% vs 5%, P < .001; thromboembolic events despite aspirin prophylaxis: 23.5% [initial LEN-DEX or crossover] vs 5%; P < .001). This trial was registered at www.clinicaltrials.gov as #NCT00064038.

Figure 1

Trial design and patient flow. PD/D indicates progressive disease or death; and AE/W, adverse event or withdrawal.

Figure 2

PFS and OS from the times of randomization and crossover with attention to the effects of cytogenetic abnormalities. (A) PFS: Estimated 1-year PFS rate was 78% with LEN + DEX and 52% with DEX (P = .0003). (B) OS: No difference is apparent between arms. (C) OS according to the presence or absence of CAs: patients without CAs had superior OS, regardless of treatment arm. No statistically significant OS differences between LEN-DEX and DEX could be demonstrated within the CA and no CA groups. Testing CA versus No CA within treatment groups: LEN-DEX, P = .09; DEX, P = .03. Testing LEN-DEX versus DEX within CA groups: CA, P = .42; No CA, P = .7. (D) PFS and OS after crossover from DEX to LEN-DEX.