engleski

Can Idarubicin circumvent multidrug resistance to chemotherapy in multiple myeloma?

Background: Poor response to chemotherapy in multiple myeloma (MM) has been associated with the development of multidrug resistance (MDR) primarily following the increase of P-glycoprotein (Pgp) expression. Therefore, the need for the new chemotherapy protocols with MDR-independent substrates has emerged. Study: Pgp phenotype and function of bone marrow cells during the follow-up of 78 consecutive MM patients, differing in the clinical stage and disease duration, had been analysed. The patients were treated according to the standard MM chemotherapy protocols, also including a small group of patients treated with VID protocol (vincristine, idarubicin, dexamethasone), MDR-independent idarubicin replacing the MDR-dependent adriamycin in standard VAD protocol. Results: Pgp expression on plasma cells increased with clinical stage of disease: the highest in clinical stage III (p<0.046). On the same cell population, the MDR-dependent treatment increased Pgp expression (p<0.003). The plasma cell population expressing Pgp increased with the lack of response to treatment (CR vs. NR p<0.023), and with the fatal outcome (p<0.001), associating the size of the plasma cell population to the seriousness of the patients&#8217; condition. Despite their high Pgp expression, the patients on VID protocol had significantly (p<0.005) smaller plasma cell population, further decreasing with the duration of the VID therapy (p<0.001). Conclusion: Although, as it seems, both VAD and VID develop MDR, and the Pgp-mediated efflux in MM patients on VAD and VID may not differ considerably, VID appears to have a much stronger effect on suppression of the expanded clone of plasma cells in patients with MM that could explain a good response to therapy in MM patients on VID. Our preliminary results indicate that idarubicin may circumvent MDR and increase of cytotoxic effect of chemotherapy. The modified VAD protocol increases intracellular drug concentration and might enhance chemotherapeutic efficacy of the treatment.

Pgp; Multiple myeloma

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