REVLIMID maintenance therapy extended progression-free survival ( PFS ) vs placebo in two pivotal studies

• In Study 1 ( US ), median PFS at unblinding * was 2.8 years for REVLIMID vs 1.6 years for placebo ( HR 0.38 ; 95 % CI 0.27 , 0.54 ; P < 0.001 ) 3 , 5

• In Study 2 ( EU ), median PFS at unblinding * was 3.4 years for REVLIMID vs 1.9 years for placebo ( HR 0.50 ; 95 % CI 0.39 , 0.64 ; P < 0.001 ) 3 , 5

Median PFS at Updated Analysis in Study 1 ( US ) 3 , 5 †

Survival Probability (%)

1.0

0.8

0.6

0.4

0.2

REVLIMID ( n = 231 ) Placebo ( n = 229 ) REVLIMID vs Placebo : HR 0.38 ; 95 % CI 0.28 , 0.50

( 95 % CI 1.6 , 2.5 )

( 95 % CI 4.4 , NE )

0.0 0 12 24 36 48 60 72 84 96 108 Progression-Free Survival ( Months )

PFS advantage

In Study 2 ( EU ), a 1.9 year PFS advantage was demonstrated for REVLIMID maintenance therapy at updated analysis 3 , 5 †

• Median PFS of 3.9 years ( 95 % CI 3.3 , 4.7 ) for REVLIMID maintenance therapy vs 2.0 years ( 95 % CI 1.8 , 2.3 ) for placebo ( HR 0.53 ; 95 % CI 0.44 , 0.64 )

Trial Design : Study 1 ( US ; enrolled patients aged 18-70 years ) and Study 2 ( EU ; enrolled patients aged < 65 years ) were multicenter , randomized 1:1 , double-blind , parallel-group , placebo-controlled studies conducted in newly diagnosed patients who received auto-HSCT after induction therapy within 12 months . The primary endpoint for both studies was PFS defined from randomization to the date of progression or death , whichever occurred first . Patients were randomized to REVLIMID or placebo within 90-100 days post-transplant and 90-180 days post-transplant in Studies 1 and 2 , respectively . Patients needed at least a stable disease response following hematologic recovery , and must have had CrCl ≥30 mL / min . Patients in the placebo arm of Study 1 were allowed to cross over to receive REVLIMID before disease progression ; patients in Study 2 were not recommended to cross over . Please see Prescribing Information for full patient demographics . In both studies , starting dose was REVLIMID 10 mg once daily on Days 1-28 of repeated 28-day cycles . If tolerated , dose could be increased to 15 mg once daily after 3 months in the absence of dose-limiting toxicity , and treatment was to be continued until disease progression or patient withdrawal for another reason . Dose was reduced , interrupted , and / or discontinued as needed to manage toxicities . A dose increase to 15 mg once daily occurred in 135 patients ( 58 %) in Maintenance Study 1 , and in 185 patients ( 60 %) in Maintenance Study 2 .

ADVERSE REACTIONS

The most frequently reported Grade 3 or 4 reactions in ≥20 % ( REVLIMID arm ) included neutropenia , thrombocytopenia , and leukopenia . The serious adverse reactions of lung infection and neutropenia ( more than 4.5 %) occurred in the REVLIMID arm . The most frequently reported adverse reactions in ≥20 % ( REVLIMID arm ) across both maintenance studies ( Study 1 , Study 2 ) were neutropenia ( 79 %, 61 %), thrombocytopenia ( 72 %, 24 %), leukopenia ( 23 %, 32 %), anemia ( 21 %, 9 %), upper respiratory tract infection ( 27 %, 11 %), bronchitis ( 5 %, 47 %), nasopharyngitis ( 2 %, 35 %), cough ( 10 %, 27 %), gastroenteritis ( 0 %, 23 %), diarrhea ( 55 %, 39 %), rash ( 32 %, 8 %), fatigue ( 23 %, 11 %), asthenia ( 0 %, 30 %), muscle spasm ( 0 %, 33 %), and pyrexia ( 8 %, 21 %)

SELECTED SAFETY INFORMATION : CONTRAINDICATIONS

Pregnancy : REVLIMID can cause fetal harm when administered to a pregnant female and is contraindicated in females who are pregnant . If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug , the patient should be apprised of the potential risk to the fetus

Allergic Reactions : REVLIMID is contraindicated in patients who have demonstrated hypersensitivity ( e . g ., angioedema , Stevens-Johnson syndrome , toxic epidermal necrolysis ) to lenalidomide