CLINICAL NEWS
RESONATE-17 Study : Ibrutinib Safe and Effective for Patients With Relapsed / Refractory Del17p Chronic Lymphocytic Leukemia
Patients with chronic lymphocytic leukemia ( CLL ) with 17p deletion
( del17p ) have a poorer prognosis and worse overall survival ( OS ) than patients with non-del17p CLL . Previous research has shown that the Bruton tyrosine kinase inhibitor ibrutinib is effective in patients with del17p CLL or small lymphocytic
Table 6 : 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 |
System Organ Class / Preferred Term |
REVLIMID / Dex # |
Placebo / Dex # |
|
( N = 353 ) |
( N = 350 ) |
|
n (%) |
n (%) |
Eye Disorders Cataract |
6 ( 1.7 ) |
1 ( 0.3 ) |
Cataract Unilateral |
5 ( 1.4 ) |
0 ( 0.0 ) |
Psychiatric Disorder Depression |
10 ( 2.8 ) |
6 ( 1.7 ) |
Table 7 : Serious Adverse Reactions Reported in ≥1 % Patients |
and With a ≥1 % Difference in Proportion of Patients Between the |
REVLIMID / dexamethasone and Placebo / dexamethasone Groups |
System Organ Class / Preferred Term |
REVLIMID / Dex & |
Placebo / Dex & |
|
( N = 353 ) |
( N = 350 ) |
|
n (%) |
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 Pain
|
4 ( 1.1 ) |
0 ( 0.0 ) |
For Tables 5 , 6 and 7 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 Boxed Warning , Warnings |
and Precautions ( 5.4 )] |
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
6.2 Postmarketing Experience The following adverse drug reactions have been identified from the worldwide post-marketing experience with REVLIMID : Allergic conditions ( angioedema , SJS , TEN ), tumor lysis syndrome ( TLS ) and tumor flare reaction ( TFR ), pneumonitis , hepatic failure , including fatality , toxic hepatitis , cytolytic hepatitis , cholestatic hepatitis , and mixed cytolytic / cholestatic hepatitis and transient abnormal liver laboratory tests . 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 Section ( 5.7 to 5.10 )].
Cases of hypothyroidism and hyperthyroidism have also been reported . Optimal control of thyroid function is recommended before start of treatment . Baseline and ongoing monitoring of thyroid function is recommended .
7 DRUG INTERACTIONS Results from human in vitro studies show that REVLIMID is neither metabolized by nor inhibits or induces the cytochrome P450 pathway suggesting that lenalidomide is not likely to cause or be subject to P450-based metabolic drug interactions .
7.1 Digoxin When digoxin was co-administered with multiple doses of REVLIMID ( 10 mg / day ) the digoxin C max and AUC 0-∞ were increased by 14 %. Periodic monitoring of digoxin plasma levels , in accordance with clinical judgment and based on standard clinical practice in patients receiving this medication , is recommended during administration of REVLIMID .
7.2 Concomitant Therapies That May Increase the Risk of Thrombosis Erythropoietic agents , or other agents that may increase the risk of thrombosis , such as estrogen containing therapies , should be used with caution after making a benefit-risk assessment in patients receiving
REVLIMID [ see Warnings and Precautions ( 5.4 )].
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