The multicenter experience with bendamustine in the treatment of relapsed and refractory multiple myeloma

Relapsed and refractory (R/R) multiple myeloma (MM) constitutes a specific and unmet medical need. Median survival ranges from as little as 6 to 9 months, and responses to treatment are characteristically short. In patients with R/R MM after therapy of bortezomib and/or immunomodulators a bendamustine-based treatment can be used as “salvage”.

In this retrospective analysis we have identified 32 patients with R/R MM by means of case research, have been bendamustine-based treated at Hematological Clinics of Russian Federation since 2011. Median age was 67 (43–81) years, the female/male ratio was 2.5:1. After in median 2 (1–7) lines of prior therapy patients received in median 3 (1–9) cycles of bendamustine-based therapy. Bendamustine dosage was 70–120 mg/m2 /day on 2 days of each 28-day cycle until progressive disease or intolerability. Overall rate response was 56.2 %: 21.9 % partial response, stable disease 34.4 %. Median time to progression was 5.3 (0.8–18.0) months and median overall survival was 25.4 (0.8–47.1) months. Hematologic toxicity was in 53.2 % of patients.

1. Gentile M., Recchia A.G., Mazzoneetal C. et al. Perspectives in the treatment of multiple myeloma. Expert Opin Biol Ther 2013;13(1):1–22.

2. Бессмельцев С.С., Стельмашенко Л.В., Карягина Е.В. и др. Бортезомиб (Велкейд) в индукционной терапии множественной миеломы. Клиническая онкогематология 2008;1(4):315–22. [Bessmeltsev S.S., Stelmashenko L.V., Kariagina E.V. et al. Bortezomib (Velcade) for initial treatment of multiple myeloma. Klinicheskaya onkogematologiya = Clinical Oncohematology 2008;1(4):315–22. (In Russ.)].

3. Kristinsson S.Y., Landgren O., Dickman P.W. et al. Patterns of survival in multiple myeloma: a population based study of patients diagnosed in Sweden. J Clin Oncol 2007;25:1993–9.

4. Бессмельцев С.С., Стельмашенко Л.В., Карягина Е.В и др. Лечение пожилых пациентов с множественной миеломой на современном этапе. Онкогематология 2010;4:6–13. [Bessmeltsev S.S., Stelmashenko L.V., Kariagina E.V. et al. Modern strategies in therapy of elderly patients with multiple myelomа. Onkogematologiya = Oncohematology 2010;4:6–13. (In Russ.)].

5. Pocock N. Bendamustine for the fourthline treatment of multiple myeloma. London cancer new drugs group rapid review, 2013. 7 p.

6. Kalaycio M. Clinical experience with Bendamustine: A new treatment for patients with chronic lymphocytic leukemia. Clin Leukemia 2008;2(4):223–9.

7. Lorenzo L. The Alkylating Properties of Bendamustine. Clin Adv Hematol Oncol 2011;9(8):3–5.

8. Knop S., Straka C., Haen M. et al. The efficacy and toxicity of bendamustine in recurrent multiple myeloma after highdose chemotherapy. Haematologica 2005;90:1287–8.

9. Michael M., Bruns I., Bölke E. et al. Bendamustine in patients with relapsed or refractory multiple myeloma. Eur J Med Res 2010;15(1):13–9.

10. Ponisch W., Bourgeois M., Moll B. et al. Combined bendamustine, prednisone and bortezomib (BPV) in patients with relapsed or refractory multiple myeloma. J Cancer Res Clin Oncol 2012;139:499–508.

11. Heinz L., Hedwig K., Clemens L. Bendamustine-bortezomib-dexamethasone is an active and well-tolerated regimen in patients with relapsed or refractory multiple myeloma. Blood 2014;123(7):985–91.

12. Rodon P., Hulin C., Pegourie B. et al. Bendamustine, bortezomib, anddexamethasone (BVD) in elderly patients with relapsed/refractory multiple myeloma (RRMM): The Intergroupe Francophone du Myélome (IFM) 2009-01 protocol. J Clin Oncol 2012;30;аbstr 8014.

13. http://grls.rosminzdrav.ru/ImgInstr.aspx?folder=ScanVavilova &Filepath=Ne_trebuet_vneseniaNet_ND_IZM437575IP_IZM&idReg=38926&isOld=1&fileType=jpg&pfolder=2.

14. Абдулкадыров К.М., Волошин С.В., Шмидт А.В., Шуваев В.А. Эффективность бортезомиба при лечении больных рецидивирующей и рефрактерной множественной миеломой (анализ российских данных исследования eVOBS). Гематология и трансфузиология 2012;57(3): 22–5. [Abdulkadyrov K.M., Voloshin S.V., Schmidt A.V., Shuvaev V.A. Bortezomib efficiency in patients with relapsing and refractory multiple myeloma (analysis of the Russian data of EVOBS). Gematologiya i transfuziologiya = Hematology and Transfusiology 2012;57(3):22–5. (In Russ.)].

15. Mikhael J.R., Dingli D., Roy V. et al. Management of newly diagnosed symptomatic multiple myeloma: updated Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) Consensus Guidelines 2013. Mayo Clin Proc 2013;88(7):360–76.

16. Волошин С.В., Шмидт А.В., Гарифуллин А.Д. и др. Бендамустин в лечении рецидивирующей/рефрактерной множественной миеломы. Гематология и трансфузиология 2014;59(1):83. [Voloshin S.V., Schmidt A.V., Garifullin A.D. et al. Bendamustine in treatment of relapsed and refractory multiple myeloma. Gematologiya i transfuziologiya = Hematology and Transfusiology 2014;59(1):83. (In Russ.)].

17. Damaj G., Malard F., Hulin C. et al. Efficacy of bendamustine in relapsed/refractory myeloma patients: results from the French compassionate use program. Leuk Lymphoma 2012;53(4):632–4.

18. Ludwig H., Kasparu H., Leitgeb C. et al. Bendamustine-bortezomib-dexamethasone is an active and well-tolerated regimen in patients with relapsed or refractory multiple myeloma. Blood 2014;123(7):985–91.

19. Lentzsch S., O'Sullivan A., Kennedy R.C. et al. Combination of bendamustine, lenalidomide, and dexamethasone (BLD) in patients with relapsed or refractory multiple myeloma is feasible and highly effective: results of phase 1/2 open-label, dose escalation study. Blood 2012;119(20):4608–13.

20. Durie B.G.M., Harousseau J.L., Miguel J.S. et al. International uniform response criteria for multiple myeloma. Leukemia 2006;20:1467–73.

21. Ponisch W., Wiesler J., Leibleinetal S. et al. Successful mobilization of peripheral blood stem cells after intensive bendamustine pretreatment in patients with multiple myeloma. Blood 2010;116;аbstr 4439.

22. Грицаев С.В., Кузяева А.А., Волошин С.В. и др. Заготовка трансплантата для аутологичной трансплантации гемопоэтических стволовых клеток онкогематологическим больным: частота и причины неудачных сборов. РМЖ. Приложение. Онкология 2013;4(1):30–5. [Gritsaev S.V., Kuzyaeva А.А., Voloshin S.V. et al. Separation of transplant for autologous stem cells transplantation by oncohematological patients: frequency and reasons of unsuccessful collecting. RMJ. Appendix. Oncologiya = Oncology 2013;4(1): 30–5. (In Russ.)].

23. Savarese D.M.F. Common terminology criteria for adverse events. Version 4.0. National Cancer Institute, 2009. 194 p.