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Revlimid

Last reviewed on RxList: 3/6/2017
Revlimid Side Effects Center

Medical Editor: John P. Cunha, DO, FACOEP

Last reviewed on RxList 9/22/2015

Revlimid (lenalidomide) is a thalidomide analogue indicated for the treatment of patients with anemia and multiple myeloma. Revlimid is also used in patients with myelodysplastic syndrome and may also be used for other purposes not listed. Revlimid is available in generic form. Side effects of Revlimid include nausea, diarrhea, constipation, dry or itchy skin, runny or stuffy nose, muscle or joint pain, headache, or tiredness. Serious side effects of Revlimid include fetal risk, hematologic toxicity, deep vein thrombosis, and pulmonary embolism.

Our Revlimid (lenalidomide) Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Revlimid Consumer Information

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have a serious side effect such as:

Call your doctor at once if you have any of these serious side effects:

  • chest pain, sudden shortness of breath, coughing up blood;
  • pain or swelling in your arm, thigh, or calf;
  • easy bruising, unusual bleeding or weakness;
  • fever, chills, body aches, flu symptoms;
  • lower back pain, blood in your urine;
  • urinating less than usual or not at all;
  • numbness or tingly feeling around your mouth;
  • muscle weakness, tightness, or contraction, overactive reflexes;
  • fast or slow heart rate, weak pulse, feeling short of breath, confusion, fainting;
  • severe blistering, peeling, and red skin rash; or
  • the first sign of any skin rash, no matter how mild.

Less serious side effects may include:

  • nausea, diarrhea, constipation;
  • dry or itchy skin;
  • runny or stuffy nose;
  • muscle or joint pain;
  • headache; or
  • tiredness.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the entire detailed patient monograph for Revlimid (Lenalidomide)

Revlimid Professional Information

SIDE EFFECTS

The following adverse reactions are described in detail in other sections of the prescribing information:

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Newly Diagnosed MM – REVLIMID Combination Therapy:

Data were evaluated from 1613 patients in a large phase 3 study who received at least one dose of REVLIMID with low dose dexamethasone (Rd) given for 2 different durations of time (i.e., until progressive disease [Arm Rd Continuous; N=532] or for up to eighteen 28-day cycles [72 weeks, Arm Rd18; N=540] or who received melphalan, prednisone and thalidomide (Arm MPT; N=541) for a maximum of twelve 42-day cycles (72 weeks). The median treatment duration in the Rd Continuous arm was 80.2 weeks (range 0.7 to 246.7) or 18.4 months (range 0.16 to 56.7).

In general, the most frequently reported adverse reactions were comparable in Arm Rd Continuous and Arm Rd18, and included diarrhea, anemia, constipation, peripheral edema, neutropenia, fatigue, back pain, nausea, asthenia, and insomnia. 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.

In the Rd Continuous arm, the most common adverse reactions leading to dose interruption of REVLIMID were infection events (28.8%); overall, the median time to the first dose interruption of REVLIMID was 7 weeks. The most common adverse reactions leading to dose reduction of REVLIMID in the Rd Continuous arm were hematologic events (10.7%); overall, the median time to the first dose reduction of REVLIMID was 16 weeks. In the Rd Continuous arm, the most common adverse reactions leading to discontinuation of REVLIMID were infection events (3.4%).

In both Rd arms, the frequencies of onset of adverse reactions were generally highest in the first 6 months of treatment and then the frequencies decreased over time or remained stable throughout treatment, except for cataracts. The frequency of onset of cataracts increased over time with 0.7% during the first 6 months and up to 9.6% by the 2nd year of treatment with Rd Continuous.

Table 4 summarizes the adverse reactions reported for the Rd Continuous, Rd18, and MPT treatment arms.

Table 4: All Adverse Reactions in ≥5.0% and Grade 3/4 Adverse Reactions in ≥ 1.0% of Patients in the Rd Continuous or Rd18 Arms*

Body System
Adverse Reaction
All Adverse Reactions3 Grade 3/4 Adverse Reactionsb
Rd Continuous
(N = 532)
Rd18
(N = 540)
MPT
(N = 541)
Rd Continuous
(N = 532)
Rd18
(N = 540)
MPT
(N = 541)
General disorders and administration site conditions
  Fatigue%173 (32.5)177 (32.8)154 (28.5)39 ( 7.3)46 ( 8.5)31 ( 5.7)
  Asthenia150 (28.2)123 (22.8)124 (22.9)41 ( 7.7)33 ( 6.1)32 ( 5.9)
  Pyrexiac114 (21.4)102 (18.9)76 (14.0)13 ( 2.4)7( 1.3)7( 1.3)
  Non-cardiac chest pain f29 ( 5.5)31 ( 5.7)18 ( 3.3)<1%< 1%< 1%
Gastrointestinal disorders
  Diarrhea242 (45.5)208 (38.5)89 (16.5)21 ( 3.9)18 ( 3.3)8 ( 1.5)
  Abdominal pain% f109 (20.5)78 (14.4)60 (11.1)7 ( 1.3)9 ( 1.7)< 1%
  Dyspepsia f57 (10.7)28 ( 5.2)36 ( 6.7)<1%< 1%0 ( 0.0)
Musculoskeletal and connective tissue disorders
  Back painc170 (32.0)145 (26.9)116 (21.4)37 ( 7.0)34 ( 6.3)28 ( 5.2)
  Muscle spasms f109 (20.5)102 (18.9)61 (11.3)< 1%< 1%< 1%
  Arthralgia f101 (19.0)71(13.1)66 (12.2)9 ( 1.7)8 ( 1.5)8 ( 1.5)
  Bone pain f87 (16.4)77 (14.3)62 (11.5)16 ( 3.0)15 ( 2.8)14 ( 2.6)
  Pain in extremity f79 (14.8)66 (12.2)61 (11.3)8 ( 1.5)8 ( 1.5)7( 1.3)
  Musculoskeletal pain f67 (12.6)59 (10.9)36 ( 6.7)< 1%< 1%< 1%
  Musculoskeletal chest pain f60 (11.3)51 ( 9.4)39 ( 7.2)6 ( 1.1)< 1%< 1%
  Muscular weakness f43 ( 8.1)35 ( 6.5)29 ( 5.4)< 1%8 ( 1.5)< 1%
  Neck pain f40 ( 7.5)19 ( 3.5)10 ( 1.8)< 1%< 1%< 1%
Infections and infestations
  Bronchitisc90 (16.9)59 (10.9)43 ( 7.9)9 ( 1.7)6 ( 1.1)3 ( 0.6)
  Nasopharyngitis f80 (15.0)54 (10.0)33 ( 6.1)0 ( 0.0)0 ( 0.0)0 ( 0.0)
  Urinary tract infection f76 (14.3)63 (11.7)41 ( 7.6)8 ( 1.5)8 ( 1.5)< 1%
  Upper respiratory tract infectionc% f69 (13.0)53 ( 9.8)31 ( 5.7)< 1%8 ( 1.5)< 1%
  Pneumoniac ®93 (17.5)87(16.1)56 (10.4)60 (11.3)57 (10.5)41 ( 7.6)
  Respiratory tract infection%35 ( 6.6)25 ( 4.6)21 ( 3.9)7( 1.3)4( 0.7)1 ( 0.2)
  Influenza f33 ( 6.2)23 ( 4.3)15 ( 2.8)< 1%< 1%0 ( 0.0)
  Gastroenteritis f32 ( 6.0)17 ( 3.1)13 ( 2.4)0 ( 0.0)< 1%< 1%
  Lower respiratory tract infection29 ( 5.5)14 ( 2.6)16 ( 3.0)10 ( 1.9)3 ( 0.6)3 ( 0.6)
  Rhinitis f29 ( 5.5)24 ( 4.4)14 ( 2.6)0 ( 0.0)0 ( 0.0)0 ( 0.0)
  Cellulitisc< 5%< 5%< 5%8 ( 1.5)3 ( 0.6)2 ( 0.4)
  Sepsisc @33 ( 6.2)26 ( 4.8)18 ( 3.3)26 ( 4.9)20 ( 3.7)13 ( 2.4)
Nervous system disorders
  Headache f75 (14.1)52 ( 9.6)56 (10.4)< 1%< 1%< 1%
  Dysgeusia f39 ( 7.3)45 ( 8.3)22 ( 4.1)< 1%0 ( 0.0)< 1%
Blood and lymphatic system disordersd
  Anemia233 (43.8)193 (35.7)229 (42.3)97 (18.2)85 (15.7)102 (18.9)
  Neutropenia186 (35.0)178 (33.0)328 (60.6)148 (27.8)143 (26.5)243 (44.9)
  Thrombocytopenia104 (19.5)100 (18.5)135 (25.0)44 ( 8.3)43 ( 8.0)60 (11.1)
  Febrile neutropenia7( 1.3)17 ( 3.1)15 ( 2.8)6 ( 1.1)16 ( 3.0)14 ( 2.6)
  Pancytopenia5 ( 0.9)6 ( 1.1)7( 1.3)1 ( 0.2)3 ( 0.6)5 ( 0.9)
Respiratory, thoracic and mediastinal disorders
  Cough f121 (22.7)94 (17.4)68 (12.6)< 1%< 1%< 1%
  Dyspneac,e117 (22.0)89 (16.5)113 (20.9)30 ( 5.6)22 ( 4.1)18 ( 3.3)
  Epistaxis f32 ( 6.0)31 ( 5.7)17 ( 3.1)< 1%< 1%0 ( 0.0)
  Oropharyngeal pain f30 ( 5.6)22 ( 4.1)14 ( 2.6)0 ( 0.0)0 ( 0.0)0 ( 0.0)
  Dyspnea exertional e27 ( 5.1)29 ( 5.4)< 5%6 ( 1.1)2 ( 0.4)0 ( 0.0)
Metabolism and nutrition disorders
  Decreased appetite123 (23.1)115 (21.3)72 (13.3)14 ( 2.6)7 ( 1.3)5 ( 0.9)
  Hypokalemia%91 (17.1)62 (11.5)38 ( 7.0)35 ( 6.6)20 ( 3.7)11 ( 2.0)
  Hyperglycemia62 (11.7)52 ( 9.6)19 ( 3.5)28 ( 5.3)23 ( 4.3)9 ( 1.7)
  Hypocalcemia57(10.7)56 (10.4)31 ( 5.7)23 ( 4.3)19 ( 3.5)8 ( 1.5)
  Dehydration%25 ( 4.7)29 ( 5.4)17 ( 3.1)8 ( 1.5)13 ( 2.4)9 ( 1.7)
  Gout e< 5%< 5%< 5%8 ( 1.5)0 ( 0.0)0 ( 0.0)
  Diabetes mellitus% e< 5%< 5%< 5%8 ( 1.5)4 ( 0.7)2 ( 0.4)
  Hypophosphatemia e< 5%< 5%< 5%7 ( 1.3)3 ( 0.6)1 ( 0.2)
  Hyponatremia% e< 5%< 5%< 5%7( 1.3)13 ( 2.4)6 ( 1.1)
Skin and subcutaneous tissue disorders
  Rash139 (26.1)151 (28.0)105 (19.4)39 ( 7.3)38 ( 7.0)33 ( 6.1)
  Pruritus f47 ( 8.8)49 ( 9.1)24 ( 4.4)< 1%< 1%< 1%
Psychiatric disorders
  Insomnia147 (27.6)127 (23.5)53 ( 9.8)4( 0.8)6 ( 1.1)0 ( 0.0)
  Depression58 (10.9)46 ( 8.5)30 ( 5.5)10 ( 1.9)4( 0.7)1 ( 0.2)
Vascular disorders
  Deep vein thrombosisc %55 (10.3)39 ( 7.2)22 ( 4.1)30 ( 5.6)20 ( 3.7)15 ( 2.8)
  Hypotensionc %51 ( 9.6)35 ( 6.5)36 ( 6.7)11 ( 2.1)8 ( 1.5)6 ( 1.1)
Injury, Poisoning, and Procedural Complications
  Fall f43 ( 8.1)25 ( 4.6)25 ( 4.6)< 1%6 ( 1.1)6 ( 1.1)
  Contusion f33 ( 6.2)24 ( 4.4)15 ( 2.8)< 1%< 1%0 ( 0.0)
Eye disorders
  Cataract73 (13.7)31 ( 5.7)5 ( 0.9)31 ( 5.8)14 ( 2.6)3 ( 0.6)
  Cataract subcapsular e< 5%< 5%< 5%7( 1.3)0 ( 0.0)0 ( 0.0)
Investigations
  Weight decreased72 (13.5)78 (14.4)48 ( 8.9)11 ( 2.1)4( 0.7)4 ( 0.7)
Cardiac disorders
  Atrial fibrillationc37 ( 7.0)25 ( 4.6)25 ( 4.6)13 ( 2.4)9 ( 1.7)6 ( 1.1)
  Myocardial infarction (including acute)c ,e< 5%< 5%< 5%10 ( 1.9)3 ( 0.6)5 ( 0.9)
Renal and Urinary disorders
  Renal failure (including acute)c @,f49 ( 9.2)54 (10.0)37 ( 6.8)28 ( 5.3)33 ( 6.1)29 ( 5.4)
Neoplasms benign, malignant and unspecified (Incl cysts and polyps)
  Squamous cell carcinomac e< 5%< 5%< 5%8 ( 1.5)4 ( 0.7)0 ( 0.0)
  Basal cell carcinomac e,f< 5%< 5%< 5%< 1%< 1%0 ( 0.0)
Note: A subject with multiple occurrences of an adverse reaction is counted only once under the applicable Body System/Adverse Reaction.
a All treatment-emergent adverse reactions in at least 5.0% of subjects in the Rd Continuous or Rd18 Arms and at least a 2.0% higher frequency (%) in either the Rd Continuous or Rd18 Arms compared to the MPT Arm.
b All grade 3 or 4 treatment-emergent adverse reactions in at least 1.0% of subjects in the Rd Continuous or Rd18 Arms and at least a 1.0% higher frequency (%) in either the Rd Continuous or Rd18 Arms compared to the MPT Arm.
c Serious treatment-emergent adverse reactions in at least 1.0% of subjects in the Rd Continuous or Rd18 Arms and at least a 1.0% higher frequency (%) in either the Rd Continuous or Rd18 Arms compared to the MPT Arm.
d Preferred terms for the blood and lymphatic system disorders body system were included by medical judgment as known adverse reactions for Rd Continuous/Rd18, and have also been reported as serious.
e Footnote “a” not applicable
f Footnote “b” not applicable.
@ - adverse reactions in which at least one resulted in a fatal outcome
% - adverse reactions in which at least one was considered to be life threatening (if the outcome of the reaction was death, it is included with death cases)
*Adverse reactions include in combined adverse reaction terms:
Abdominal Pain: Abdominal pain, abdominal pain upper, abdominal pain lower, gastrointestinal pain
Pneumonias: Pneumonia, lobar pneumonia, pneumonia pneumococcal, bronchopneumonia, pneumocystis jiroveci pneumonia, pneumonia legionella, pneumonia staphylococcal, pneumonia klebsiella, atypical pneumonia, pneumonia bacterial, pneumonia escherichia, pneumonia streptococcal, pneumonia viral
Sepsis: Sepsis, septic shock, urosepsis, escherichia sepsis, neutropenic sepsis, pneumococcal sepsis, staphylococcal sepsis, bacterial sepsis, meningococcal sepsis, enterococcal sepsis, klebsiella sepsis, pseudomonal sepsis
Rash: Rash, rash pruritic, rash erythematous, rash maculo-papular, rash generalised, rash papular, exfoliative rash, rash follicular, rash macular, drug rash with eosinophilia and systemic symptoms, erythema multiforme, rash pustular
Deep Vein Thrombosis: Deep vein thrombosis, venous thrombosis limb, venous thrombosis

Newly Diagnosed MM - REVLIMID Maintenance Therapy Following Auto-HSCT:

Data were evaluated from 1018 patients in two randomized trials who received at least one dose of REVLIMID 10 mg daily as maintenance therapy after auto-HSCT until progressive disease or unacceptable toxicity, The mean treatment duration for REVLIMID treatment was 30.3 months for Maintenance Study 1 and 24.0 months for Maintenance Study 2 (overall range across both studies from 0.1 to 108 months). As of the cut-off date of 1 Mar 2015, 48 patients (21%) in the Maintenance Study 1 REVLIMID arm were still on treatment and none of the patients in the Maintenance Study 2 REVLIMID arm were still on treatment at the same cut-off date

The adverse reactions listed from Maintenance Study 1 included events reported post-transplant (completion of high-dose melphalan /auto-HSCT), and the maintenance treatment period. In Maintenance Study 2, the adverse reactions were from the maintenance treatment period only. In general, the most frequently reported adverse reactions (more than 20% in the REVLIMID arm) across both studies were neutropenia, thrombocytopenia, leukopenia, anemia, upper respiratory tract infection, bronchitis, nasopharyngitis, cough, gastroenteritis, diarrhea, rash, fatigue, asthenia, muscle spasm and pyrexia. The most frequently reported Grade 3 or 4 reactions (more than 20% in the REVLIMID arm) included neutropenia, thrombocytopenia, and leukopenia. The serious adverse reactions lung infection and neutropenia (more than 4.5%) occurred in the REVLIMID arm.

For REVLIMID, the most common adverse reactions leading to dose interruption were hematologic events (29.7%, data available in Maintenance Study 2 only). The most common adverse reaction leading to dose reduction of REVLIMID were hematologic events (17.7%, data available in Maintenance Study 2 only). The most common adverse reactions leading to discontinuation of REVLIMID were thrombocytopenia (2.7%) in Maintenance Study 1 and neutropenia (2.4%) in Maintenance Study 2.

The frequencies of onset of adverse reactions were generally highest in the first 6 months of treatment and then the frequencies decreased over time or remained stable throughout treatment.

Table 5 summarizes the adverse reactions reported for the REVLIMID and placebo maintenance treatment arms.

Table 5: All Adverse Reactions in ≥5.0% and Grade 3/4 Adverse Reactions in ≥ 1.0% of Patients in the REVLIMID Vs Placebo Arms*

Body System
Adverse Reaction
Maintenance Study 1 Maintenance Study 2
All Adverse Reactions [a] Grade 3/4 Adverse Reactions [b] All Adverse Reactions [a] Grade 3/4 Adverse Reactions [b]
REVLIMID
(N=224)
n (%)
Placebo
(N=221)
n (%)
REVLIMID
(N=224)
n (%)
Placebo
(N=221)
n (%)
REVLIMID
(N=293)
n (%)
Placebo
(N=280)
n (%)
REVLIMID
(N=293)
n (%)
Placebo
(N=280)
n (%)
Blood and lymphatic system disorders
Neutropenia c % 177 ( 79.0)94 ( 42.5)133 ( 59.4)73 ( 33.0)178 ( 60.8)33 ( 11.8)158 ( 53.9)21 ( 7.5)
Thrombocytopenia c % 162 ( 72.3)101 ( 45.7)84 ( 37.5)67 ( 30.3)69 ( 23.5)29 ( 10.4)38 ( 13.0)8 ( 2.9)
Leukopenia c51 ( 22.8)25 ( 11.3)45 ( 20.1)22 ( 10.0)93 ( 31.7)21 ( 7.5)71 ( 24.2)5 ( 1.8)
Anemia47 ( 21.0)27 ( 12.2)23 ( 10.3)18 ( 8.1)26 ( 8.9)15 ( 5.4)11 ( 3.8)3 ( 1.1)
Lymphopenia40 ( 17.9)29 ( 13.1)37 ( 16.5)26 ( 11.8)13 ( 4.4)3 ( 1.1)11 ( 3.8)2 ( 0.7)
Pancytopenia c d % 1 ( 0.4)0 ( 0.0)0 ( 0.0)0 ( 0.0)12 ( 4.1)1 ( 0.4)7( 2.4)1 ( 0.4)
Febrile neutropenia c39 ( 17.4)34 ( 15.4)39 ( 17.4)34 ( 15.4)7 ( 2.4)1 ( 0.4)5 ( 1.7)1 ( 0.4)
Infections and infestations#
Upper respiratory tract infection e60 ( 26.8)35 ( 15.8)7( 3.1)9 ( 4.1)32 ( 10.9)18 ( 6.4)1 ( 0.3)0 ( 0.0)
Neutropenic infection40 ( 17.9)19 ( 8.6)27 ( 12.1)14 ( 6.3)0 ( 0.0)0 ( 0.0)0 ( 0.0)0 ( 0.0)
Pneumonias* c % 31 ( 13.8)15 ( 6.8)23 ( 10.3)7( 3.2)50 ( 17.1)13 ( 4.6)27 ( 9.2)5 ( 1.8)
Bronchitis c10 ( 4.5)9 ( 4.1)1 ( 0.4)5 ( 2.3)139 ( 47.4)104 ( 37.1)4( 1.4)1 ( 0.4)
Nasopharyngitis e5 ( 2.2)2 ( 0.9)0 ( 0.0)0 ( 0.0)102 ( 34.8)84 ( 30.0)1 ( 0.3)0 ( 0.0)
Gastroenteritis c0 ( 0.0)0 ( 0.0)0 ( 0.0)0 ( 0.0)66 ( 22.5)55 ( 19.6)6 ( 2.0)0 ( 0.0)
Rhinitis e2 ( 0.9)0 ( 0.0)0 ( 0.0)0 ( 0.0)44 ( 15.0)19 ( 6.8)0 ( 0.0)0 ( 0.0)
Sinusitis e8 ( 3.6)3 ( 1.4)0 ( 0.0)0 ( 0.0)41 ( 14.0)26 ( 9.3)0 ( 0.0)1 ( 0.4)
Influenza c8 ( 3.6)5 ( 2.3)2 ( 0.9)1 ( 0.5)39 ( 13.3)19 ( 6.8)3 ( 1.0)0 ( 0.0)
Lung infection c21 ( 9.4)2 ( 0.9)19 ( 8.5)2 ( 0.9)9 ( 3.1)4( 1.4)1 ( 0.3)0 ( 0.0)
Lower respiratory tract infection e13 ( 5.8)5 ( 2.3)6 ( 2.7)4 ( 1.8)4 ( 1.4)4( 1.4)0 ( 0.0)2 ( 0.7)
Infection c12 ( 5.4)6 ( 2.7)9 ( 4.0)5 ( 2.3)17 ( 5.8)5 ( 1.8)0 ( 0.0)0 ( 0.0)
Urinary tract infection c d e9 ( 4.0)5 ( 2.3)4( 1.8)4( 1.8)22 ( 7.5)17 ( 6.1)1 ( 0.3)0 ( 0.0)
Lower respiratory tract infection bacterial d6 ( 2.7)1 ( 0.5)4( 1.8)0 ( 0.0)0 ( 0.0)0 ( 0.0)0 ( 0.0)0 ( 0.0)
Bacteremia d5 ( 2.2)0 ( 0.0)4( 1.8)0 ( 0.0)0 ( 0.0)0 ( 0.0)0 ( 0.0)0 ( 0.0)
Herpes zoster c d11 ( 4.9)10 ( 4.5)3 ( 1.3)2 ( 0.9)29 ( 9.9)25 ( 8.9)6 ( 2.0)2 ( 0.7)
Sepsis* c d @ 2 ( 0.9)1 ( 0.5)0 ( 0.0)0 ( 0.0)6 ( 2.0)1 ( 0.4)4 ( 1.4)1 ( 0.4)
Gastrointestinal disorders
Diarrhea122 ( 54.5)83 ( 37.6)22 ( 9.8)17 ( 7.7)114 ( 38.9)34 ( 12.1)7 ( 2.4)0 ( 0.0)
Nausea e33 ( 14.7)22 ( 10.0)16 ( 7.1)10 ( 4.5)31 ( 10.6)28 ( 10.0)0 ( 0.0)0 ( 0.0)
Vomiting17 ( 7.6)12 ( 5.4)8 ( 3.6)5 ( 2.3)16 ( 5.5)15 ( 5.4)1 ( 0.3)0 ( 0.0)
Constipation e12 ( 5.4)8 ( 3.6)0 ( 0.0)0 ( 0.0)37 ( 12.6)25 ( 8.9)2 ( 0.7)0 ( 0.0)
Abdominal pain e8 ( 3.6)7( 3.2)1 ( 0.4)4 ( 1.8)31 ( 10.6)15 ( 5.4)1 ( 0.3)1 ( 0.4)
Abdominal pain upper e0 ( 0.0)0 ( 0.0)0 ( 0.0)0 ( 0.0)20 ( 6.8)12 ( 4.3)1 ( 0.3)0 ( 0.0)
General disorders and administration site conditions
Asthenia0 ( 0.0)1 ( 0.5)0 ( 0.0)0 ( 0.0)87 ( 29.7)53 ( 18.9)10 ( 3.4)2 ( 0.7)
Fatigue51 ( 22.8)30 ( 13.6)21 ( 9.4)9 ( 4.1)31 ( 10.6)15 ( 5.4)3 ( 1.0)0 ( 0.0)
Pyrexia e17 ( 7.6)10 ( 4.5)2 ( 0.9)2 ( 0.9)60 ( 20.5)26 ( 9.3)1 ( 0.3)0 ( 0.0)
Skin and subcutaneous tissue disorders
Dry skin e9 ( 4.0)4 ( 1.8)0 ( 0.0)0 ( 0.0)31 ( 10.6)21 ( 7.5)0 ( 0.0)0 ( 0.0)
Rash71 ( 31.7)48 ( 21.7)11 ( 4.9)5 ( 2.3)22 ( 7.5)17 ( 6.1)3 ( 1.0)0 ( 0.0)
Pruritus9 ( 4.0)4 ( 1.8)3 ( 1.3)0 ( 0.0)21 ( 7.2)25 ( 8.9)2 ( 0.7)0 ( 0.0)
Nervous system disorders
Paresthesia e2 ( 0.9)0 ( 0.0)0 ( 0.0)0 ( 0.0)39 ( 13.3)30 ( 10.7)1 ( 0.3)0 ( 0.0)
Peripheral neuropathy* e34 ( 15.2)30 ( 13.6)8 ( 3.6)8 ( 3.6)29 ( 9.9)15 ( 5.4)4 ( 1.4)2 ( 0.7)
Headache d11 ( 4.9)8 ( 3.6)5 ( 2.2)1 ( 0.5)25 ( 8.5)21 ( 7.5)0 ( 0.0)0 ( 0.0)
Investigations
Alanine aminotransferase increased16 ( 7.1)3 ( 1.4)8 ( 3.6)0 ( 0.0)5 ( 1.7)5 ( 1.8)0 ( 0.0)1 ( 0.4)
Aspartate aminotransferase increased d 13 ( 5.8)5 ( 2.3)6 ( 2.7)0 ( 0.0)2 ( 0.7)5 ( 1.8)0 ( 0.0)0 ( 0.0)
Metabolism and nutrition disorders
Hypokalemia24 ( 10.7)13 ( 5.9)16 ( 7.1)12 ( 5.4)12 ( 4.1)1 ( 0.4)2 ( 0.7)0 ( 0.0)
Dehydration9 ( 4.0 )5 ( 2.3)7 ( 3.1)3 ( 1.4)0 ( 0.0)0 ( 0.0)0 ( 0.0)0 ( 0.0)
Hypophosphatemia d16 ( 7.1)15 ( 6.8)13 ( 5.8)14 ( 6.3)0 ( 0.0)1 ( 0.4)0 ( 0.0)0 ( 0.0)
Musculoskeletal and connective tissue disorders
Muscle spasms e0 ( 0.0)1 ( 0.5)0 ( 0.0)0 ( 0.0)98 ( 33.4)43 ( 15.4)1 ( 0.3)0 ( 0.0)
Myalgia e7 ( 3.1)8 ( 3.6)3 ( 1.3)5 ( 2.3)19 ( 6.5)12 ( 4.3)2 ( 0.7)1 ( 0.4)
Musculoskeletal paine1 ( 0.4)1 ( 0.5)0 ( 0.0)0 ( 0.0)19 ( 6.5)11 ( 3.9)0 ( 0.0)0 ( 0.0)
Hepatobiliary disorders
Hyperbilirubinemia e34 ( 15.2)19 ( 8.6)4( 1.8)2 ( 0.9)4( 1.4)1 ( 0.4)2 ( 0.7)0 ( 0.0)
Respiratory, thoracic and mediastinal disorders
Cough e23 ( 10.3)12 ( 5.4)3 ( 1.3)1 ( 0.5)80 ( 27.3)56 ( 20.0)0 ( 0.0)0 ( 0.0)
Dyspnea c e15 ( 6.7)9 ( 4.1)8 ( 3.6)4 ( 1.8)17 ( 5.8)9 ( 3.2)2 ( 0.7)0 ( 0.0)
Rhinorrhea e0 ( 0.0)3 ( 1.4)0 ( 0.0)0 ( 0.0)15 ( 5.1)6 ( 2.1)0 ( 0.0)0 ( 0.0)
Pulmonary embolism c d e0 ( 0.0)0 ( 0.0)0 ( 0.0)0 ( 0.0)3 ( 1.0)0 ( 0.0)2 ( 0.7)0 ( 0.0)
Vascular disorders
Deep vein thrombosis* c d %8 ( 3.6)2 ( 0.9)5 ( 2.2)2 ( 0.9)7 ( 2.4)1 ( 0.4)4 ( 1.4)1 ( 0.4)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Myelodysplastic syndrome c d e5 ( 2.2)0 ( 0.0)2 ( 0.9)0 ( 0.0)3 ( 1.0)0 ( 0.0)1 ( 0.3)0 ( 0.0)
Note: AEs are coded to body system /adverse reaction using MedDRA v15.1. A subject with multiple occurrences of an AE is counted only once in each AE category.
a All treatment-emergent AEs in at least 5% of patients in the Lenalidomide Maintenance group and at least 2% higher frequency (%) than the Placebo Maintenance group.
b All grade 3 or 4 treatment-emergent AEs in at least 1% of patients in the Lenalidomide Maintenance group and at least 1% higher frequency (%) than the Placebo Maintenance group.
c All serious treatment-emergent AEs in at least 1% of patients in the Lenalidomide Maintenance group and at least 1% higher frequency (%) than the Placebo Maintenance group.
d Footnote “a” not applicable for either study
e Footnote “b” not applicable for either study
@ -ADRs where at least one resulted in a fatal outcome
% - ADRs where at least one was considered to be Life Threatening (if the outcome of the event was death, it is included with death cases)
# - All adverse reactions under Body System of Infections and Infestation except for rare infections of Public Health interest will be considered listed
*Adverse Reactions for combined ADR terms (based on relevant TEAE PTs included in Maintenance Studies 1 and 2 [per MedDRA v 15.1]):
Pneumonias Bronchopneumonia,. Lobar pneumonia, Pneumocystis jiroveci pneumonia, Pneumonia, Pneumonia klebsiella, Pneumonia legionella, Pneumonia mycoplasmal, Pneumonia pneumococcal, Pneumonia streptococcal, Pneumonia viral, Lung disorder, Pneumonitis
Sepsis: Bacterial sepsis, Pneumococcal sepsis, Sepsis, Septic shock, Staphylococcal sepsis
Peripheral neuropathy: Neuropathy peripheral, Peripheral motor neuropathy, Peripheral sensory neuropathy, Polyneuropathy
Deep vein thrombosis: Deep vein thrombosis, Thrombosis, Venous thrombosis

After At Least One Prior Therapy For MM

Data were evaluated from 703 patients in two studies who received at least one dose of REVLIMID/dexamethasone (353 patients) or placebo/dexamethasone (350 patients).

In the REVLIMID/dexamethasone treatment group, 269 patients (76%) had at least one dose interruption with or without a dose reduction of REVLIMID compared to 199 patients (57%) in the placebo/dexamethasone treatment group. Of these patients who had one dose interruption with or without a dose reduction, 50% in the REVLIMID/dexamethasone treatment group had at least one additional dose interruption with or without a dose reduction compared to 21% in the placebo/dexamethasone treatment group. Most adverse reactions and Grade 3/4 adverse reactions were more frequent in patients who received the combination of REVLIMID/dexamethasone compared to placebo/dexamethasone.

Tables 6, 7, and 8 summarize the adverse reactions reported for REVLIMID/dexamethasone and placebo/dexamethasone groups.

Table 6: Adverse Reactions Reported in ≥5% of Patients and with a ≥2% Difference in Proportion of Patients Between the REVLIMID/dexamethasone and Placebo/dexamethasone Groups

Body System
Adverse Reaction
REVLIMID/Dex*
(N=353)
n (%)
Placebo/Dex *
(N=350)
n (%)
Blood and lymphatic system disorders
Neutropenia%149 (42.2)22 ( 6.3)
Anemia@111 (31.4)83 (23.7)
Thrombocytopenia@76 (21.5)37 (10.6)
Leukopenia28 ( 7.9)4( 1.1)
Lymphopenia19 ( 5.4)5 ( 1.4)
General disorders and administration site conditions
Fatigue155 (43.9)146 (41.7)
Pyrexia97 (27.5)82 (23.4)
Peripheral edema93 (26.3)74 (21.1)
Chest Pain29 ( 8.2)20 ( 5.7)
Lethargy24 ( 6.8)8 ( 2.3)
Gastrointestinal disorders
Constipation143 (40.5)74 (21.1)
Diarrhea@136 (38.5)96 (27.4)
Nausea@92 (26.1)75 (21.4)
Vomiting@43 (12.2)33 ( 9.4)
Abdominal Pain@35 ( 9.9)22 ( 6.3)
Dry Mouth25 ( 7.1)13 ( 3.7)
Musculoskeletal and connective tissue disorders
Muscle cramp118 (33.4)74 (21.1)
Back pain91 (25.8)65 (18.6)
Bone Pain48 (13.6)39 (11.1)
Pain in Limb42 (11.9)32 ( 9.1)
Nervous system disorders
Dizziness82 (23.2)59 (16.9)
Tremor75 (21.2)26 ( 7.4)
Dysgeusia54 (15.3)34 ( 9.7)
Hypoaesthesia36 (10.2)25 ( 7.1)
Neuropathya 23 ( 6.5)13 ( 3.7)
Respiratory, Thoracic and Mediastinal Disorders
Dyspnea83 (23.5)60 (17.1)
Nasopharyngitis62 (17.6)31 ( 8.9)
Pharyngitis48 (13.6)33 ( 9.4)
Bronchitis40 (11.3)30 ( 8.6)
Infectionsb and infestations
Upper respiratory tract infection87 (24.6)55 (15.7)
Pneumonia@48 (13.6)29 ( 8.3)
Urinary Tract Infection30 ( 8.5)19 ( 5.4)
Sinusitis26 ( 7.4)16 ( 4.6)
Skin and subcutaneous system disorders
Rashc75 (21.2)33 ( 9.4)
Sweating Increased35 ( 9.9)25 ( 7.1)
Dry Skin33 ( 9.3)14 ( 4.0)
Pruritus27 ( 7.6)18 ( 5.1)
Metabolism and nutrition disorders
Anorexia55 (15.6)34 ( 9.7)
Hypokalemia48 (13.6)21 ( 6.0)
Hypocalcemia31 ( 8.8)10 ( 2.9)
Appetite Decreased24 ( 6.8)14 ( 4.0)
Dehydration23 ( 6.5)15 ( 4.3)
Hypomagnesemia24 ( 6.8)10 ( 2.9)
Investigations
Weight Decreased69 (19.5)52 (14.9)
Eye disorders
Blurred vision61 (17.3)40 (11.4)
Vascular disorders
Deep vein thrombosis%33 ( 9.3)15 ( 4.3)
Hypertension28 ( 7.9)20 ( 5.7)
Hypotension25 ( 7.1)15 ( 4.3)

Table 7: Grade 3/4 Adverse Reactions Reported in ≥2% Patients and With a ≥1% Difference in Proportion of Patients Between the REVLIMID/dexamethasone and Placebo/dexamethasone groups

Body System
Adverse Reaction
REVLIMID/Dex#
(N=353)
n (%)
Placebo/Dex#
(N=350)
n (%)
Blood and lymphatic system disorders
Neutropenia%118 (33.4)12 ( 3.4)
Thrombocytopenia@43 (12.2)22 ( 6.3)
Anemia@35 ( 9.9)20 ( 5.7)
Leukopenia14 ( 4.0)1 ( 0.3)
Lymphopenia10 ( 2.8)4 ( 1.1)
Febrile Neutropenia%8 ( 2.3)0 ( 0.0)
General disorders and administration site conditions
Fatigue23 ( 6.5)17 ( 4.9)
Vascular disorders
Deep vein thrombosis0029 ( 8.2)12 ( 3.4)
Infections and infestations
Pneumonia@30 ( 8.5)19 ( 5.4)
Urinary Tract Infection5 ( 1.4)1 ( 0.3)
Metabolism and nutrition disorders
Hypokalemia17 ( 4.8)5 ( 1.4)
Hypocalcemia13 ( 3.7)6 ( 1.7)
Hypophosphatemia9 ( 2.5)0 ( 0.0)
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism@14 ( 4.0)3 ( 0.9)
Respiratory Distress@4 ( 1.1)0 ( 0.0)
Musculoskeletal and connective tissue disorders
Muscle weakness20 ( 5.7)10 ( 2.9)
Gastrointestinal disorders
Diarrhea@11 ( 3.1)4 ( 1.1)
Constipation7 ( 2.0)1 ( 0.3)
Nausea@6 ( 1.7)2 ( 0.6)
Cardiac disorders
Atrial fibrillation@13(3.7)4 ( 1.1)
Tachycardia6 ( 1.7)1 ( 0.3)
Cardiac Failure Congestive@5 ( 1.4)1 ( 0.3)
Nervous System disorders
Syncope10 ( 2.8)3 ( 0.9)
Dizziness7 ( 2.0)3 ( 0.9)
Eye Disorders
Cataract6 ( 1.7)1 ( 0.3)
Cataract Unilateral5 ( 1.4)0 ( 0.0)
Psychiatric Disorder
Depression10 ( 2.8)6 ( 1.7)

Table 8: Serious Adverse Reactions Reported in ≥1% Patients and With a ≥1% Difference in Proportion of Patients Between the REVLIMID/dexamethasone and Placebo/dexamethasone Groups

Body System Adverse Reaction REVLIMID/Dex&
(N=353)
n (%)
Placebo/Dex&
(N=350)
n (%)
Blood and lymphatic system disorders
Febrile Neutropenia%6 ( 1.7)0 ( 0.0)
Vascular disorders
Deep vein thrombosis%26 ( 7.4)11 ( 3.1)
Infections and infestations
Pneumonia@33 ( 9.3)21 ( 6.0)
Respiratory, thoracic, and mediastinal disorders
Pulmonary embolism@13 ( 3.7)3 ( 0.9)
Cardiac disorders
Atrial fibrillation@11 ( 3.1)2 ( 0.6)
Cardiac Failure Congestive@5 ( 1.4)0 ( 0.0)
Nervous system disorders
Cerebrovascular accident@7 ( 2.0)3 ( 0.9)
Gastrointestinal disorders
Diarrhea @6 ( 1.7)2 ( 0.6)
Musculoskeletal and connective tissue disorders
Bone Pain4 ( 1.1)0 ( 0.0)
For Tables 6, 7 and 8 above:
@ - adverse reactions in which at least one resulted in a fatal outcome
% - adverse reactions in which at least one was considered to be life threatening (if the outcome of the reaction was death, it is included with death cases)
Median duration of exposure among patients treated with REVLIMID/dexamethasone was 44 weeks while median duration of exposure among patients treated with placebo/dexamethasone was 23 weeks. This should be taken into consideration when comparing frequency of adverse reactions between two treatment groups REVLIMID/dexamethasone vs. placebo/dexamethasone.

Venous And Arterial Thromboembolism [see BOX WARNING, WARNINGS AND PRECAUTIONS]

VTE and ATE are increased in patients treated with REVLIMID.

Deep vein thrombosis (DVT) was reported as a serious (7.4%) or severe (8.2%) adverse drug reaction at a higher rate in the REVLIMID/dexamethasone group compared to 3.1 % and 3.4% in the placebo/dexamethasone group, respectively in the 2 studies in patients with at least 1 prior therapy with discontinuations due to DVT adverse reactions reported at comparable rates between groups. In the NDMM study, DVT was reported as an adverse reaction (all grades: 10.3%, 7.2%, 4.1%), as a serious adverse reaction (3.6%, 2.0%, 1.7%), and as a Grade 3/4 adverse reaction (5.6%, 3.7%, 2.8%) in the Rd Continuous, Rd18, and MPT Arms, respectively. Discontinuations and dose reductions due to DVT adverse reactions were reported at comparable rates between the Rd Continuous and Rd18 Arms (both <1%). Interruption of REVLIMID treatment due to DVT adverse reactions was reported at comparable rates between the Rd Continuous (2.3%) and Rd18 (1.5%) arms. Pulmonary embolism (PE) was reported as a serious adverse drug reaction (3.7%) or Grade 3/4 (4.0%) at a higher rate in the REVLIMID/dexamethasone group compared to 0.9% (serious or grade 3/4) in the placebo/dexamethasone group in the 2 studies in patients with, at least 1 prior therapy, with discontinuations due to PE adverse reactions reported at comparable rates between groups. In the NDMM study, the frequency of adverse reactions of PE was similar between the Rd Continuous, Rd18, and MPT Arms for adverse reactions (all grades: 3.9%, 3.3%, and 4.3%, respectively), serious adverse reactions (3.8%, 2.8%, and 3.7%, respectively), and grade 3/4 adverse reactions (3.8%, 3.0%, and 3.7%, respectively).

Myocardial infarction was reported as a serious (1.7%) or severe (1.7%) adverse drug reaction at a higher rate in the REVLIMID/dexamethasone group compared to 0.6 % and 0.6% respectively in the placebo/dexamethasone group. Discontinuation due to MI (including acute) adverse reactions was 0.8% in REVLIMID/dexamethasone group and none in the placebo/dexamethasone group. In the NDMM study, myocardial infarction (including acute) was reported as an adverse reaction (all grades: 2.4%, 0.6%, and 1.1%), as a serious adverse reaction, (2.3%, 0.6%, and 1.1%), or as a severe adverse reaction (1.9%, 0.6%, and 0.9%) in the Rd Continuous, Rd18, and MPT Arms, respectively.

Stroke (CVA) was reported as a serious (2.3%) or severe (2.0%) adverse drug reaction in the REVLIMID/dexamethasone group compared to 0.9% and 0.9% respectively in the placebo/dexamethasone group. Discontinuation due to stroke (CVA) was 1.4% in REVLIMID/ dexamethasone group and 0.3% in the placebo/dexamethasone group. In the NDMM study, CVA was reported as an adverse reaction (all grades: 0.8%, 0.6%, and 0.6%), as a serious adverse reaction (0.8%, 0.6 %, and 0.6%), or as a severe adverse reaction (0.6%, 0.6%, 0.2%) in the Rd Continuous, Rd18, and MPT arms respectively.

Other Adverse Reactions: After At Least One Prior Therapy For MM

In these 2 studies, the following adverse drug reactions (ADRs) not described above that occurred at ≥1% rate and of at least twice of the placebo percentage rate were reported:

Blood and lymphatic system disorders: pancytopenia, autoimmune hemolytic anemia

Cardiac disorders: bradycardia, myocardial infarction, angina pectoris

Endocrine disorders: hirsutism Eye disorders: blindness, ocular hypertension

Gastrointestinal disorders: gastrointestinal hemorrhage, glossodynia

General disorders and administration site conditions: malaise

Investigations: liver function tests abnormal, alanine aminotransferase increased

Nervous system disorders: cerebral ischemia

Psychiatric disorders: mood swings, hallucination, loss of libido

Reproductive system and breast disorders: erectile dysfunction

Respiratory, thoracic and mediastinal disorders: cough, hoarseness

Skin and subcutaneous tissue disorders: exanthem, skin hyperpigmentation

Myelodysplastic Syndromes

A total of 148 patients received at least 1 dose of 10 mg REVLIMID in the del 5q MDS clinical study. At least one adverse event was reported in all of the 148 patients who were treated with the 10 mg starting dose of REVLIMID. The most frequently reported adverse events were related to blood and lymphatic system disorders, skin and subcutaneous tissue disorders, gastrointestinal disorders, and general disorders and administrative site conditions.

Thrombocytopenia (61.5%; 91/148) and neutropenia (58.8%; 87/148) were the most frequently reported adverse events. The next most common adverse events observed were diarrhea (48.6%; 72/148), pruritus (41.9%; 62/148), rash (35.8%; 53/148) and fatigue (31.1%; 46/148). Table 9 summarizes the adverse events that were reported in ≥ 5% of the REVLIMID treated patients in the del 5q MDS clinical study. Table 10 summarizes the most frequently observed Grade 3 and Grade 4 adverse reactions regardless of relationship to treatment with REVLIMID. In the single-arm studies conducted, it is often not possible to distinguish adverse events that are drug-related and those that reflect the patient’s underlying disease.

Table 9: Summary of Adverse Events Reported in ≥5% of the REVLIMID Treated Patients in del 5q MDS Clinical Study

Body System
Adverse Event [a]
10 mg Overall
(N=148)
Patients with at least one adverse event148 (100.0)
Blood and Lymphatic System Disorders
  Thrombocytopenia91(61.5)
  Neutropenia87(58.8)
  Anemia17(11.5)
  Leukopenia12(8.1)
  Febrile Neutropenia8(5.4)
Skin and Subcutaneous Tissue Disorders
  Pruritus62(41.9)
  Rash53(35.8)
  Dry Skin21(14.2)
  Contusion12(8.1)
  Night Sweats12(8.1)
  Sweating Increased10(6.8)
  Ecchymosis8(5.4)
Erythema8(5.4)
Gastrointestinal Disorders
  Diarrhea72(48.6)
  Constipation35(23.6)
  Nausea35(23.6)
  Abdominal Pain18(12.2)
  Vomiting15(10.1)
  Abdominal Pain Upper12(8.1)
  Dry Mouth10(6.8)
  Loose Stools9(6.1)
Respiratory, Thoracic and Mediastinal Disorders
  Nasopharyngitis34(23.0)
  Cough29(19.6)
  Dyspnea25(16.9)
  Pharyngitis23(15.5)
  Epistaxis22(14.9)
  Dyspnea Exertional10(6.8)
  Rhinitis10(6.8)
  Bronchitis9(6.1)
General Disorders and Administration Site Conditions
  Fatigue 46 (31.1)
  Pyrexia 31 (20.9)
  Edema Peripheral 30 (20.3)
  Asthenia 22 (14.9)
  Edema 15 (10.1)
  Pain 10 (6.8)
  Rigors 9 (6.1)
  Chest Pain 8 (5.4)
Musculoskeletal and Connective Tissue Disorders
  Arthralgia32(21.6)
  Back Pain31(20.9)
  Muscle Cramp27(18.2)
  Pain in Limb16(10.8)
  Myalgia13(8.8)
  Peripheral Swelling12(8.1)
Nervous System Disorders
  Dizziness29(19.6)
  Headache29(19.6)
  Hypoesthesia10(6.8)
  Dysgeusia9(6.1)
  Peripheral Neuropathy8(5.4)
Infections and Infestations
  Upper Respiratory Tract Infection22(14.9)
  Pneumonia17(11.5)
  Urinary Tract Infection16(10.8)
  Sinusitis12(8.1)
  Cellulitis8(5.4)
Metabolism and Nutrition Disorders
  Hypokalemia16(10.8)
  Anorexia15(10.1)
  Hypomagnesemia9(6.1)
Investigations
  Alanine Aminotransferase Increased12(8.1)
  Psychiatric Disorders
  Insomnia15(10.1)
  Depression8(5.4)
Renal and Urinary Disorders
  Dysuria10(6.8)
Vascular Disorders
  Hypertension9( 6.1)
Endocrine Disorders
  Acquired Hypothyroidism10(6.8)
Cardiac Disorders
  Palpitations8(5.4)
[a] Body System and adverse events are coded using the MedDRA dictionary. Body System and adverse events are listed in descending order of frequency for the Overall column. A patient with multiple occurrences of an AE is counted only once in the AE category

Table 10: Most Frequently Observed Grade 3 and 4 Adverse Events [1] Regardless of Relationship to Study Drug Treatment

Adverse Events [2] 10 mg
(N=148)
Patients with at least one Grade 3/4 AE131 (88.5)
  Neutropenia79(53.4)
  Thrombocytopenia74(50.0)
  Pneumonia11(7.4)
  Rash10(6.8)
  Anemia9(6.1)
  Leukopenia8(5.4)
  Fatigue7(4.7)
  Dyspnea7(4.7)
  Back Pain7(4.7)
  Febrile Neutropenia6(4.1)
  Nausea6(4.1)
  Diarrhea5(3.4)
  Pyrexia5(3.4)
  Sepsis4(2.7)
  Dizziness4(2.7)
  Granulocytopenia3(2.0)
  Chest Pain3(2.0)
  Pulmonary Embolism3(2.0)
  Respiratory Distress3(2.0)
  Pruritus3(2.0)
  Pancytopenia3(2.0)
  Muscle Cramp3(2.0)
  Respiratory Tract Infection2(1.4)
  Upper Respiratory Tract Infection2(1.4)
  Asthenia2(1.4)
  Multi-organ Failure2(1.4)
  Epistaxis2(1.4)
  Hypoxia2(1.4)
  Pleural Effusion2(1.4)
  Pneumonitis2(1.4)
  Pulmonary Hypertension2(1.4)
  Vomiting2(1.4)
  Sweating Increased2(1.4)
  Arthralgia2(1.4)
  Pain in Limb2(1.4)
  Headache2(1.4)
  Syncope2(1.4)
[1] Adverse events with frequency ≥1% in the 10 mg Overall group. Grade 3 and 4 are based on National Cancer Institute Common Toxicity Criteria version 2.
[2] Adverse events are coded using the MedDRA dictionary. A patient with multiple occurrences of an AE is counted only once in the adverse event category.

In other clinical studies of REVLIMID in MDS patients, the following serious adverse events (regardless of relationship to study drug treatment) not described in Table 9 or 10 were reported:

Blood and lymphatic system disorders: warm type hemolytic anemia, splenic infarction, bone marrow depression, coagulopathy, hemolysis, hemolytic anemia, refractory anemia

Cardiac disorders: cardiac failure congestive, atrial fibrillation, angina pectoris, cardiac arrest, cardiac failure, cardio-respiratory arrest, cardiomyopathy, myocardial infarction, myocardial ischemia, atrial fibrillation aggravated, bradycardia, cardiogenic shock, pulmonary edema, supraventricular arrhythmia, tachyarrhythmia, ventricular dysfunction

Ear and labyrinth disorders: vertigo

Endocrine disorders: Basedow’s disease

Gastrointestinal disorders: gastrointestinal hemorrhage, colitis ischemic, intestinal perforation, rectal hemorrhage, colonic polyp, diverticulitis, dysphagia, gastritis, gastroenteritis, gastroesophageal reflux disease, obstructive inguinal hernia, irritable bowel syndrome, melena, pancreatitis due to biliary obstruction, pancreatitis, perirectal abscess, small intestinal obstruction, upper gastrointestinal hemorrhage General disorders and administration site conditions: disease progression, fall, gait abnormal, intermittent pyrexia, nodule, rigors, sudden death

Hepatobiliary disorders: hyperbilirubinemia, cholecystitis, acute cholecystitis, hepatic failure

Immune system disorders: hypersensitivity

Infections and infestations: infection bacteremia, central line infection, clostridial infection, ear infection, Enterobacter sepsis, fungal infection, herpes viral infection NOS, influenza, kidney infection, Klebsiella sepsis, lobar pneumonia, localized infection, oral infection, Pseudomonas infection, septic shock, sinusitis acute, sinusitis, Staphylococcal infection, urosepsis

Injury, poisoning and procedural complications: femur fracture, transfusion reaction, cervical vertebral fracture, femoral neck fracture, fractured pelvis, hip fracture, overdose, post procedural hemorrhage, rib fracture, road traffic accident, spinal compression fracture

Investigations: blood creatinine increased, hemoglobin decreased, liver function tests abnormal, troponin I increased

Metabolism and nutrition disorders: dehydration, gout, hypernatremia, hypoglycemia

Musculoskeletal and connective tissue disorders: arthritis, arthritis aggravated, gouty arthritis, neck pain, chondrocalcinosis pyrophosphate

Neoplasms benign, malignant and unspecified: acute leukemia, acute myeloid leukemia, bronchoalveolar carcinoma, lung cancer metastatic, lymphoma, prostate cancer metastatic

Nervous system disorders: cerebrovascular accident, aphasia, cerebellar infarction, cerebral infarction, depressed level of consciousness, dysarthria, migraine, spinal cord compression, subarachnoid hemorrhage, transient ischemic attack

Psychiatric disorders: confusional state

Renal and urinary disorders: renal failure, hematuria, renal failure acute, azotemia, calculus ureteric, renal mass

Reproductive system and breast disorders: pelvic pain

Respiratory, thoracic and mediastinal disorders: bronchitis, chronic obstructive airways disease exacerbated, respiratory failure, dyspnea exacerbated, interstitial lung disease, lung infiltration, wheezing

Skin and subcutaneous tissue disorders: acute febrile neutrophilic dermatosis

Vascular system disorders: deep vein thrombosis, hypotension, aortic disorder, ischemia, thrombophlebitis superficial, thrombosis

Mantle Cell Lymphoma

In the MCL trial, a total of 134 patients received at least 1 dose of REVLIMID. Their median age was 67 (range 43-83) years, 128/134 (96%) were Caucasian, 108/134 (81%) were males and 82/134 (61%) had duration of MCL for at least 3 years.

Table 11 summarizes the most frequently observed adverse reactions regardless of relationship to treatment with REVLIMID. Across the 134 patients treated in this study, median duration of treatment was 95 days (1-1002 days). Seventy-eight patients (58%) received 3 or more cycles of therapy, 53 patients (40%) received 6 or more cycles, and 26 patients (19%) received 12 or more cycles. Seventy-six patients (57%) underwent at least one dose interruption due to adverse events, and 51 patients (38%) underwent at least one dose reduction due to adverse events. Twenty-six patients (19%) discontinued treatment due to adverse events.

Table 11: Incidence of Adverse Reactions (≥10%) or Grade 3 / 4 AE (in at least 2 patients) in Mantle Cell Lymphoma

Body System Adverse Reaction All AEs1 (N=134)
n (%)
Grade 3/4 AEs2 (N=134)
n (%)
General disorders and administration site conditions
Fatigue45 (34)9 ( 7)
Pyrexia$31 (23)3 ( 2)
Edema peripheral21(16)0
Asthenia$19 (14)4 ( 3)
General physical health deterioration3 ( 2)2 ( 1)
Gastrointestinal disorders
Diarrhea$42 (31)8 ( 6)
Nausea$40 (30)1 (<1)
Constipation21 (16)1 (<1)
Vomiting$16 (12)1 (<1)
Abdominal pain$13 (10)5 ( 4)
Musculoskeletal and connective tissue disorders
Back pain18(13)2 ( 1)
Muscle spasms17(13)1 (<1)
Arthralgia11 ( 8)2 ( 1)
Muscular weakness$8 ( 6)2 ( 1)
Respiratory, thoracic and mediastinal disorders
Cough38 (28)1 (<1)
Dyspnea$24 (18)8 ( 6)
Pleural Effusion10 ( 7)2 ( 1)
Hypoxia3 ( 2)2 ( 1)
Pulmonary embolism3 ( 2)2 ( 1)
Respiratory distress$2 ( 1)2 ( 1)
Oropharyngeal pain13 (10)0
Infections and infestations
Pneumonia@ $19 (14)12 ( 9)
Upper respiratory tract infection17 (13)0
Cellulitis*3 ( 2)2 ( 1)
Bacteremia$ 2 ( 1)2 ( 1)
Staphylococcal sepsis$ 2 ( 1)2 ( 1)
Urinary tract infection$ 5 ( 4)2 ( 1)
Skin and subcutaneous tissue disorders
Rash +30 (22)2 ( 1)
Pruritus23 (17)1 (<1)
Blood and lymphatic system disorders
Neutropenia65(49)58(43)
Thrombocytopenia% $ 48 (36)37 (28)
Anemia$ 41 (31)15 (11)
Leukopenia$ 20 (15)9 ( 7)
Lymphopenia10 ( 7)5 ( 4)
Febrile neutropenia$ 8 ( 6)8 ( 6)
Metabolism and nutrition disorders
Decreased appetite19 (14)1 (<1)
Hypokalemia17 (13)3 ( 2)
Dehydration$ 10 ( 7)4 ( 3)
Hypocalcemia4 ( 3)2 ( 1)
Hyponatremia3 ( 2)3 ( 2)
Renal and urinary disorders
Renal failure$ 5 ( 4)2 ( 1)
Vascular disorders
Hypotension@ $ 9 ( 7)4 ( 3)
Deep vein thrombosis$ 5 ( 4)5 ( 4)
Neoplasms benign, malignant and unspecified (including cysts and polyps)
Tumor flare13 (10)0
Squamous cell carcinoma of skin$ 4 ( 3)4 ( 3)
Investigations
Weight decreased17 (13)0
1-MCL trial AEs – All treatment emergent AEs with >10% of subjects
2-MCL trial Grade 3/4 AEs – All treatment-emergent Grade 3/4 AEs in 2 or more subjects
$-MCL trial Serious AEs – All treatment-emergent SAEs in 2 or more subjects
@ - AEs where at least one resulted in a fatal outcome
% - AEs where at least one was considered to be Life Threatening (if the outcome of the event was death, it is included with death cases)
# - All adverse reactions under Body System of Infections except for rare infections of Public Health interest will be considered listed
+ - All adverse reactions under HLT of Rash will be considered listed

The following adverse events which have occurred in other indications and not described above have been reported (5%-10%) in patients treated with REVLIMID monotherapy for mantle cell lymphoma.

General disorders and administration site conditions: Chills

Musculoskeletal and connective tissue disorders: Pain in extremity

Nervous system disorders: Dysgeusia, headache, neuropathy peripheral

Infections and infestations: Respiratory tract infection, sinusitis, nasopharyngitis

Skin and subcutaneous tissue disorders: Dry skin, night sweats

The following serious adverse events not described above and reported in 2 or more patients treated with REVLIMID monotherapy for mantle cell lymphoma.

Respiratory, thoracic, and mediastinal disorders: Chronic obstructive pulmonary disease

Infections and infestations: Clostridium difficile colitis, sepsis

Neoplasms benign, malignant and unspecified (including cysts and polyps): Basal cell carcinoma

Cardiac disorder: Supraventricular tachycardia

Postmarketing Experience

The following adverse drug reactions have been identified from the worldwide post-marketing experience with REVLIMID. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure [see WARNINGS AND PRECAUTIONS]

Skin and subcutaneous tissue disorders: Stevens-Johnson Syndrome, toxic epidermal necrolysis

Immune system disorders: Angioedema, acute graft-versus-host disease (following allogeneic hematopoietic transplant)

Neoplasms benign, malignant and unspecified (incl cysts and polyps): Tumor lysis syndrome, tumor flare reaction

Respiratory, thoracic and mediastinal disorders: Pneumonitis

Hepatobiliary disorders: Hepatic failure (including fatality), toxic hepatitis, cytolytic hepatitis, cholestatic hepatitis, mixed cytolytic/cholestatic hepatitis, transient abnormal liver laboratory tests

Infections and infestations: Viral reactivation (such as hepatitis B virus and herpes zoster)

Endocrine disorders: Hypothyroidism, hyperthyroidism

Read the entire FDA prescribing information for Revlimid (Lenalidomide)

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© Revlimid Patient Information is supplied by Cerner Multum, Inc. and Revlimid Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

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