WARNINGS AND PRECAUTIONS (continued)
treatment arm. REVLIMID is not indicated and not recommended for use in CLL
outside of controlled clinical trials
Second Primary Malignancies: In clinical trials in patients with MM receiving
REVLIMID, an increase of invasive second primary malignancies (SPM) notably
AML and MDS have been observed. The increase of AML and MDS occurred
predominantly in NDMM patients receiving REVLIMID in combination with oral
melphalan (5.3%) or immediately following high dose intravenous melphalan and
ASCT (up to 5.2%). The frequency of AML and MDS cases in the REVLIMID/dex
arms was observed to be 0.4%. Cases of B-cell malignancies (including Hodgkin’s
Lymphomas) were observed in clinical trials where patients received REVLIMID in the
post-ASCT setting. Patients who received REVLIMID-containing therapy until disease
progression did not show a higher incidence of invasive SPM than patients treated in
the fixed duration REVLIMID-containing arms. Monitor patients for the development
of second primary malignancies. Take into account both the potential benefit of
REVLIMID and risk of second primary malignancies when considering treatment
Hepatotoxicity: Hepatic failure, including fatal cases, has occurred in patients
treated with REVLIMID in combination with dex. The mechanism of drug-induced
hepatotoxicity is unknown. Pre-existing viral liver disease, elevated baseline liver
enzymes, and concomitant medications may be risk factors. Monitor liver enzymes
periodically. Stop REVLIMID upon elevation of liver enzymes. After return to baseline
values, treatment at a lower dose may be considered
Allergic Reactions: Angioedema and serious dermatologic reactions including
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been
reported. These events can be fatal. Patients with a prior history of Grade 4 rash
associated with thalidomide treatment should not receive REVLIMID. REVLIMID
interruption or discontinuation should be considered for Grade 2-3 skin rash.
REVLIMID must be discontinued for angioedema, Grade 4 rash, exfoliative or
bullous rash, or if SJS or TEN is suspected and should not be resumed following
discontinuation for these reactions. REVLIMID capsules contain lactose. Risk-benefit
of REVLIMID treatment should be evaluated in patients with lactose intolerance
Tumor Lysis Syndrome: Fatal instances of tumor lysis syndrome (TLS) have been
reported during treatment with lenalidomide. The patients at risk of TLS are those
with high tumor burden prior to treatment. These patients should be monitored
closely and appropriate precautions taken
Tumor Flare Reaction: Tumor flare reaction (TFR) has occurred during
investigational use of lenalidomide for CLL and lymphoma, and is 6