Although expression of the Mr 170,000 P-glycoprotein drug pump is likely to play a role in multidrug resistance (MDR) in haematological malignancies, it is now evident that other MDR mechanisms may be operational as well in leukaemias, lymphomas, and multiple myeloma.
Recently, clinical reversal of MDR by noncytotoxic P-gp modulators such as verapamil, cyclosporin A (CsA), and PSC 833 was explored in acute leukemia and multiple myeloma.
CDy1 efflux may therefore be a useful assay to determine whether high expression of ABCB1 is predictive of poor clinical responses in MM patients treated with carfilzomib.
Genotyping for ABCB1 1236C>T, 2677G>A/T, and 3435C>T polymorphisms was performed, and the effects of ABCB1 polymorphisms on AUC<sub>0-24</sub> for lenalidomide were compared in 36 patients with MM who were administered lenalidomide according to the drug label based on CCr.
NFV and LPV restored CFZ activity at therapeutically relevant drug levels and thus represent ready-to-use drugs to be tested in clinical trials to target ABCB1 and to re-sensitize PC to established myeloma drugs, in particular CFZ.
MDR1 has been the most studied in hematological malignancies, particularly in lymphoma and multiple myeloma (MM), diseases generally considered as overexpressing such mechanisms in relapse.
Significant expression of MDR-1 mRNA and P-glycoprotein was not detected in 25 cases of multiple myeloma prior to chemotherapy and even after several courses of VAD (vincristine, adriamycin and dexamethasone) therapy by Northern blotting and immunostaining using monoclonal anti-P-glycoprotein antibody (MRK-16), respectively.
Studies in myelogenous leukemia and myeloma have so far provided best evidence for a significant correlation between P-glycoprotein expression and response to chemotherapy, although large discrepancies in the proportion of positive cells limit any definite conclusion.
Polymorphisms in the multiple drug resistance protein 1 and in P-glycoprotein 1 are associated with time to event outcomes in patients with advanced multiple myeloma treated with bortezomib and pegylated liposomal doxorubicin.
This study evaluated the prognostic role of MDR1 in the outcome of 115 multiple myeloma patients treated with DAV (dexamethasone, doxorubicin [adryamicin] and vincristine) regimen followed by autologous transplantation.