The primary efficacy endpoint, progression-free survival (PFS), was defined as the time from randomization to the first documentation of disease progression as determined by Independent Response Adjudication Committee (IRAC), based on International Myeloma Working Group [IMWG] criteria or death due to any cause, whichever occurred first during the study until the end of the PFS follow-up phase. For the efficacy analysis of all endpoints, the primary comparison was between Rd Continuous and MPT arms. The efficacy results are summarized in the table below. PFS was significantly longer with Rd Continuous than MPT: HR 0.72 (95% CI: 0.61-0.85 p <0.0001). A lower percentage of subjects in the Rd Continuous arm compared with the MPT arm had PFS events (52% versus 61%, respectively). The improvement in median PFS time in the Rd Continuous arm compared with the MPT arm was 4.3 months. The myeloma response rate was higher with Rd Continuous compared with MPT (75.1% versus 62.3%); with a complete response in 15.1% of Rd Continuous arm patients versus 9.3% in the MPT arm. The median time to first response was 1.8 months in the Rd Continuous arm versus 2.8 months in the MPT arm.

For the interim OS analysis with 03 March 2014 data cutoff, the median follow-up time for all surviving patients is 45.5 months, with 697 death events, representing 78% of prespecified events required for the planned final OS analysis (697/896 of the final OS events). The observed OS HR was 0.75 for Rd Continuous versus MPT (95% CI = 0.62, 0.90).

Table 12: Overview of Efficacy Results – Study MM-020 (Intent-to-treat Population)

CR = complete response; d = low-dose dexamethasone; HR = hazard ratio; IRAC = Independent Response Adjudication Committee;
M = melphalan; NE = not estimable; OS = overall survival; P = prednisone; PFS = progression-free survival; PR = partial response;
R = lenalidomide; Rd Continuous = Rd given until documentation of progressive disease; Rd18 = Rd given for ≤ 18 cycles; T = thalidomide;
VGPR = very good partial response; vs = versus.
a The median is based on the Kaplan-Meier estimate.
b The 95% Confidence Interval (CI) about the median.
c Based on Cox proportional hazards model comparing the hazard functions associated with the indicated treatment arms.
d The p-value is based on the unstratified log-rank test of Kaplan-Meier curve differences between the indicated treatment arms.
e Best assessment of response during the treatment phase of the study
f Including patients with no response assessment data or whose only assessment was “response not eva luable.”
g Data cutoff date = 24 May 2013.
h Data cutoff date = 3 March 2014.

Rd Continuous
(N = 535) Rd18
(N = 541) MPT
(N = 547)
  PFS - IRAC (months)g   
     Number of PFS events 278 (52.0) 348 (64.3) 334 (61.1)
     Mediana PFS time, months (95% CI)b 25.5 (20.7, 29.4) 20.7 (19.4, 22.0) 21.2 (19.3, 23.2)
     HR [95% CI]c; p-valued   
           Rd Continuous vs MPT 0.72 (0.61, 0.85);
<0.0001  
           Rd Continuous vs Rd18 0.70 (0.60, 0.82)   
           Rd18 vs MPT 1.03 (0.89, 1.20)  
&