Median Progression-Free Survival ( PFS )
100
80
Rd Continuous ( n = 535 ) 25.5 mo ( 95 % CI 20.7 , 29.4 ) |
Rd18 |
( n = 541 ) 20.7 mo ( 95 % CI 19.4 , 22.0 ) |
MPT |
( n = 547 ) 21.2 mo ( 95 % CI 19.3 , 23.2 ) |
Survival Probability (%) |
60
40
|
Planned duration of treatment in the Rd18 and MPT arms was 18 months |
|
Rd Continuous vs MPT Rd Continuous vs Rd18
Rd18 vs MPT
HR ( 95 % CI ) 0.72 ( 0.61 , 0.85 ) 0.70 ( 0.60 , 0.82 ) 1.03 ( 0.89 , 1.20 )
Logrank P value ( 2-sided ) P < 0.0001
28 % reduced risk of progression or death for patients receiving Rd Continuous vs MPT
|
|
20 |
|
|
0 0 1
2 3 4 5
Progression-Free Survival ( Years )
Rd Continuous Rd18 MPT |
535 541 547 |
400 391 380 |
319 319 304 |
265 265 244 |
218 167 170 |
168 108 116 |
105 56 58 |
55 30 28 |
19 7 6 |
2 2 1 |
0 0 0 |
Number of Subjects at Risk
PFS Events : Rd Continuous = 278 / 535 ( 52.0 %), Rd18 = 348 / 541 ( 64.3 %), MPT = 334 / 547 ( 61.1 %)
PFS was defi ned as the time from randomization to the fi rst 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 fi rst during the study until the end of the PFS follow-up phase .
A randomized , multicenter , open-label , 3-arm trial of 1,623 patients was conducted to compare the effi cacy and safety of REVLIMID and low-dose dexamethasone ( Rd ) given for 2 different durations of time to that of melphalan , prednisone , and thalidomide ( MPT ) in newly diagnosed MM patients who were not a candidate for stem cell transplant ( SCT ). In the fi rst arm of the study , Rd was given continuously until progressive disease ( Arm Rd Continuous ). In the second arm , Rd was given for up to eighteen 28-day cycles ( 72 weeks , Arm Rd18 ). In the third arm , melphalan , prednisone , and thalidomide ( MPT ) was given for a maximum of twelve 42-day cycles ( 72 weeks ). For the purposes of this study , a patient who was < 65 years of age was not a candidate for SCT if the patient refused to undergo SCT therapy or the patient did not have access to SCT due to the cost or other reasons . Patients were stratifi ed at randomization by age ( ≤75 versus > 75 years ), stage ( ISS Stages I and II versus Stage III ), and country .
Patients in the Rd Continuous and Rd18 arms received REVLIMID 25 mg once daily on Days 1 to 21 of 28-day cycles . Dexamethasone was dosed 40 mg once daily on Days 1 , 8 , 15 , and 22 of each 28-day cycle . For patients over 75 years old , the starting dose of dexamethasone was 20 mg orally once daily on Days 1 , 8 , 15 , and 22 of repeated 28-day cycles . Initial dose and regimens for Rd Continuous and Rd18 were adjusted according to age and renal function . All patients received prophylactic anticoagulation with the most commonly used being aspirin .
Rd Continuous until progression showed 25.5 months median PFS
SELECTED SAFETY INFORMATION : ADVERSE REACTIONS
Multiple Myeloma
• In newly diagnosed : The most frequently reported Grade 3 or 4 reactions included neutropenia , anemia , thrombocytopenia , pneumonia , asthenia , fatigue , back pain , hypokalemia , rash , cataract , lymphopenia , dyspnea , DVT , hyperglycemia , and leukopenia . The highest frequency of infections occurred in Arm Rd Continuous ( 75 %) compared to Arm MPT ( 56 %). There were more grade 3 and 4 and serious adverse reactions of infection in Arm Rd Continuous than either Arm MPT or Rd18
• The most common adverse reactions reported in ≥20 % ( Arm Rd Continuous ): diarrhea ( 46 %), anemia ( 44 %), neutropenia ( 35 %), fatigue ( 33 %), back pain ( 32 %), asthenia ( 28 %), insomnia ( 28 %), rash ( 26 %), decreased appetite ( 23 %), cough ( 23 %), dyspnea ( 22 %), pyrexia ( 21 %), abdominal pain ( 21 %), muscle spasms ( 20 %), and thrombocytopenia ( 20 %)