4.8 Undesirable effects

 a. Summary of the safety profile in patients with multiple myeloma

In two Phase III placebo-controlled studies, 353 patients with multiple myeloma were exposed to the lenalidomide/dexamethasone combination and 351 to the placebo/dexamethasone combination. The median duration of exposure to study treatment was significantly longer (44.0 weeks) in the lenalidomide/dexamethasone group as compared to placebo/dexamethasone (23.1 weeks). The difference was accounted for by a lower rate of discontinuation from study treatment due to lower progression of disease in patients exposed to lenalidomide/dexamethasone (39.7%) than in placebo/dexamethasone patients (70.4%).

325 (92%) of the patients in the lenalidomide/dexamethasone group experienced at least one adverse reaction compared to 288 (82%) in the placebo/dexamethasone group.

The most serious adverse reactions were:

• Venous thromboembolism (deep vein thrombosis, pulmonary embolism) (see section 4.4)

• Grade 4 neutropenia (see section 4.4).
The most frequently observed adverse reactions which occurred significantly more frequently in the lenalidomide/dexamethasone group compared to the placebo/dexamethasone group were neutropenia (39.4%), fatigue (27.2%), asthenia (17.6%), constipation (23.5%), muscle cramp (20.1%), thrombocytopenia (18.4%), anaemia (17.0%), diarrhoea (14.2%) and rash (10.2%).

The adverse reactions observed in patients treated with lenalidomide/dexamethasone are listed below by system organ class and frequency. Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. Frequencies are defined as: very common ( 1/10); common ( 1/100 to < 1/10); uncommon ( 1/1,000 to < 1/100); rare ( 1/10,000 to < 1/1,000), very rare (< 1/10,000 including isolated reports), unknown (cannot be estimated from the available data).

a. Tabulated summary of adverse reactions

The following table is derived from data gathered during the pivotal studies. The data were not adjusted according to the greater duration of treatment in the lenalidomide/dexamethasone versus the placebo/dexamethasone arms in the pivotal studies (See section 5.1).

Table 1: ADRs reported in clinical studies in patients with multiple myeloma treated with lenalidomide

System Organ Class/Preferred Term
 All ADRs/Frequency
 Grade 3−4 ADRs/Frequency
 
Infections and Infestations
 Very Common

Pneumonia, Upper respiratory tract infection

Common

Sepsis, Bacterial, viral and fungal infections (including opportunistic infections), Sinusitis
 Common

Pneumonia, Bacterial, viral and fungal infections (including opportunistic infections)
 
Neoplasms benign, malignant and unspecified
 Uncommon

Basal cell carcinoma
 
Blood and Lymphatic System Disorders
 Very Common

Thrombocytopenia^, Neutropenias^, Anaemia, Haemorrhagic disorder^, Leucopenias

Common

Pancytopenia

Uncommon

Haemolysis, Autoimmune haemolytic anaemia, Haemolytic anaemia
 Very Common

Thrombocytopenia^, Neutropenias^, Leu