090 Direct involvement of Bortezomib in the occurrence of heart failure

Bortezomib is an antitumor therapy for Multiple Myeloma and Non Hodgkin Lymphoma which incidence is dramatically growing up. This drug inhibits proteasome activity through action on the 26 S proteasome in mammalian cells and leads to apoptosis of tumoral cells. Cardiac toxicity of this drug is not clearly established and its mechanistic poorly understood. Moreover, the few reports in the update literature are unable to prove a direct involvement of bortezomib in the occurrence of Acute or Chronic Heart Failure.We report the first clinical observation of chronic heart failure which can be directly related to administration of bortezomib. This relationship is strongly suggested by the pharmacological Begaud's score for drug adverse events with a high degree of imputability. This observation is further supported by the report of all other cases of cardiac failure associated with bortezomib, reported in the French pharmacovigilance database (table 1).These reports, the largest cohort available in the international literature, should lead to a systematically screening for asymptomatic cardiac diseases as well as a rigorous follow up of patients exposed to bortezomib. The strength of our report is i/ the identification of a case for which the direct role of bortezomib was demonstrated, ii/ to emphasize with our case series that this effect occurs more frequently than suspected with a serious outcome.PatientsAge (Year)GenderDiseaseCardiac Risk FactorPrior Chemotherpy regimensN°bortezomib containing cyclesCumulated Dose (mg/m2)Cardiac complicationdeathImputability#179FMMHTA012,64Acute Heart FailureyesI3#279FMM01631,2Acute Heart FailureNoI1#371FMM00631,2Acute Heart FailureNoI1#454FMM0214,45Cardiogenic ShockYesI1#574MMM0013,9Acute Heart FailureYesI4#661FMMHTA41054,3Acute Heart FailureNoI1#769FMM00315,6Acute Heart FailureNoI1#854MMM05315,6Acute Heart FailureNoI1Data from the French Pharmacovigilance Databas