(N=353)
 placebo/dex

(N=351)
 
Time to Event

  Hazard ratio [95% CI],

p-value a
 
Time To Progression

Median [95% CI], weeks
 
 60.1 [44.3, 73.1]
 20.1 [17.7, 20.3]
 0.350 [0. 287, 0. 426], p < 0.001
 
Progression Free Survival

Median [95% CI], weeks
 48.1

[36. 4, 62.1]
 20.0 [16.1, 20.1]
 0.393 [0.326, 0.473]

p < 0.001
 
Overall Survival

Median [95% CI], weeks

1-year Overall Survival rate
 164.3 [145.1, 192.6]

82%
 136.4 [113.1, 161.7]

75%
 0.833 [0.687, , 1.009]

p = 0.045
 
Response rate

  Odds ratio [95% CI], p-value b
 
Overall Response [n, %]

Complete Response [n, %]

 212 (60.1)

58 (16.4)
 75 (21.4)

11 (3.1)
 
 5.53 [3.97, 7.71], p < 0.001

6.08 [3.13, 11.80], p < 0.001

a: Two-tailed log rank test comparing survival curves between treatment groups.

b: Two-tailed continuity-corrected chi-square test.

Exploratory study

An open-label, randomized, multicenter, Phase 3 study was conducted in 445 patients with newly diagnosed multiple myeloma; 222 patients were randomized to the lenalidomide/low dose dexamethasone arm, and 223 were randomized to the lenalidomide/standard dose dexamethasone arm. Patients randomized to the lenalidomide/standard dose dexamethasone arm received lenalidomide 25 mg/day, Days 1 to 21 every 28 days plus dexamethasone 40 mg/day on Days 1 to 4, 9 to 12, and 17 to 20 every 28 days for the first four cycles. Patients randomized to the lenalidomide/low dose dexamethasone arm received lenalidomide 25 mg/day, Days 1 to 21 every 28 days plus low dose dexamethasone – 40 mg/day on Days 1, 8, 15, and 22 every 28 days. In the lenalidomide/low dose dexamethasone group, 20 patients (9.1%) underwent at least one dose interruption compared to 65 patients (29.3%) in the lenalidomide/standard dose dexamethasone arm.

In a post-hoc analysis, lower mortality was observed in the lenalidomide/low dose dexamethasone arm 6.8% (15/220) compared to the lenalidomide/standard dose dexamethasone arm 19.3% (43/223), in the newly diagnosed multiple myeloma patient population, with a median follow up of 72.3 weeks.

However with a longer follow-up, the difference in overall survival in favour of low dose dexamethasone tends to decrease.

Considering that the patient population differs from the authorised indication, these results should be interpreted with caution.

5.2 Pharmacokinetic properties

 Lenalidomide has an asymmetric carbon atom and can therefore exist as the optically active forms S() and R(+). Lenalidomide is produced as a racemic mixture. Lenalidomide is generally more soluble in organic solvents but exhibits the greatest solubility in 0.1N HCl buffer.

Absorption

Lenalidomide is rapidly absorbed following oral administration in healthy volunteers, under fasting conditions, with maximum plasma concentrations occurring between 0.5 and 2 hours post-dose. In patients, as well as healthy volunteers, the maximum concentration (Cmax) and area-under-the-concentration time curve (AUC) increase proportionally with increases in dose. Multiple dosing does not cause marked drug accumulation. In plasma, the relative exposures of the S- and R- enantiome