Antitumor activity of bortesomib retreatment in relapsed or refractory multiple myeloma patients

The efficacy of re-treatment with bortezomib was evaluated in 95 patients with refractory and relapsing forms of multiple myeloma (MM) in hematology center of Novosibirsk. The median age of patients was 65 years (36–81), 4–10 courses of therapy were held. Overall objective response rate in patients retreated with bortezomib was 68.4 %. СR and nCR was achieved in 20 % of patients, a partial response (PR) was observed in 34.7 % of patients. In the group of patients treated with VD, objective response was achieved in 66.6 % of patients. Among patients treated with VMP and CVD, overall response rate was 71 % and 66.7 %, respectively. Median (Me) of prolonged response was 12 months, Me of overall survival has not been reached. The side effects of bortezomib were predicted and controlled. The most significant of them were gastrointestinal and hematology adverse events, asthenia and peripheral neuropathy. Thus, bortezomib is the high-effective remedy, playing the important role in MM therapy as the first and subsequent lines of the treatment.

1. Bessmeltsev S.S., Kariagina E.V., Stelmashenko L.V. et al. Bortezomib (Velcade) in combination with dexamethasone in the treatment of refractory/relapsing forms of multiple myeloma in elderly patients // Onkogematologiya. 2010. (2). 40–45. (in Russian)

2. Bessmeltsev S.S., Kariagina E.V., Stelmashenko L.V. et al. The frequency, characteristics and treatment of peripheral neuropathy in patients with multiple myeloma treated with bortezomib (Velcade) // Onkogematologiya. 2008. (3). 52–62. (in Russian)

3. Votjacova O.M. Actual therapy for multiple myeloma // Byulleten' sibirskoy meditsiny. 2008. (Suppl. 3). 33–41. (in Russian)

4. Pospelova T.I., Skvortsova N.V., Nechunaeva I.N. The results of Bortezomib treatment of multiple myeloma // Onkogematologiya. 2009. (2). 35–42. (in Russian)

5. Skvortsova N.V., Melnikova T.V., Melnichenko E.V. Mishenin A.V. Effectiveness of multiple myeloma targeted therapy with the use of proteasome inhibitors // Byulleten' Sibirskogo otdeleniya Rossiyskoy akademii meditsinskikh nauk. 2011. (2). 94–101. (in Russian)

6. Blade J., Samson D., Reece D. et al. Criteria for evaluating disease response and progression in patients with multiple myeloma treated by high-dose therapy and haemopoietic stem cell transplantation // Br. J. Haematol. 1998. 102. 1115–1123.

7. Karin M., Cao Y., Greten F.R., Li Z.W. NF-kB in cancer: from innocent bystander to major culprit // Nat. Rev. Cancer. 2002. 2. 301–310.

8. Kyle R.A., Rajkumar S.V. Multiple myeloma // Blood. 2008. 111. (6). 2962–2972.

9. Mitsiades N., Mitsiades C.S., Richardson P.G. et al. The proteasome inhibitor PS-341 potentiates sensitivity of multiple myeloma cells to conventional chemotherapeutic agents: therapeutic applications // Blood. 2003. 101. 2377–2380.

10. Montagut C., Rovira A., Mellado B. et al. Preclinical and clinical development of the proteasome inhibitor bortezomib in cancer treatment // Drugs Today (Barc.). 2005. 41. 299–315.

11. Richardson P.G., Barlogie B., Berenson J. еt al. A phase 2 study of bortezomib in relapsed, refractory myeloma // N. Engl. J. Med. 2003. 348. 2609–2617.

12. Richardson P.G., Britmberg H., Jagannath S. et al. Characterization and reversibility of peripheral neuropathy in patients with advanced multiple myeloma treated with bortezomib (VELCADE). The SUMMIT and CREST Study Group // Hematol. J. 2004. 5. (Suppl.). S129.

13. Smith A., Wisloff F., Samson D. UK Myeloma Forum, Nordic Myeloma Study Group and British Committee for Standards in Haematology. Guidelines on the diagnosis and management of multiple myeloma // Br. J. Haematol. 2006. 132. 410—451.