Drug Interactions between pembrolizumab and pomalidomide

GENERALLY AVOID: Coadministration of thalidomide or its analogs with a programmed death receptor-1 (PD-1) or programmed death ligand-1 (PD-L1) blocking antibody may increase the risk of mortality in patients with multiple myeloma. The mechanism has not been established. In two randomized clinical trials of patients with multiple myeloma, the addition of pembrolizumab to a regimen of thalidomide analog plus dexamethasone resulted in increased mortality and toxicity. In the first trial (n=249), investigators reported a greater than 50% increase in relative risk of death in patients with relapsed and refractory multiple myeloma receiving pomalidomide and low-dose dexamethasone with pembrolizumab compared to controls receiving the treatment without pembrolizumab. There was also an 18% increase of severe, grade 3 to 5 toxicity and 17% increase of serious adverse events relative to the control arm. In the second trial (n=301), the relative risk of death was more than doubled in newly diagnosed patients with multiple myeloma receiving lenalidomide and low-dose dexamethasone with pembrolizumab compared to controls. The incidence of severe, grade 3 to 5 toxicity was increased by 22% and serious adverse events increased by 15% relative to controls.

MANAGEMENT: Concomitant use of a PD-1 or PD-L1 blocking antibody with thalidomide or a thalidomide analog plus dexamethasone in the treatment of multiple myeloma is not recommended outside of controlled clinical trials.

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