Preview

Oncohematology

Advanced search

Efficacy of lenalidomide, bortezomib, and prednisolone in patients with relapsed or refractory multiple myeloma

https://doi.org/10.17650/1818-8346-2015-10-4-8-14

Abstract

49 patients aged 28 to 81 years old (median age of 55 years old) with relapsed or refractory multiple myeloma (MM) were enrolled in the study. The relapse was diagnosed in 25 (51 %) patients, the refractory disease was determined in 24 (49 %) patients (including primary refractory disease in 14 (28.6 %) patients). The prior therapy for all patients included bortezomib-based treatment in combination with thalidomide and autologus stem cell transplantation (8.1 %). Lenalidomide had not been used in the previous therapeutic regimens. All patients were given the original treatment regimen, which included lenalidomide, bortezomib, and prednisolone (RVP). The therapy was made up of seven induction cycles with each one lasting for 48 days. Length of courses was 14 days. After seven cycles of RVP therapy were over, such results were achieved: complete response (CR) in 1 (2 %) patient; very good partial response (VGPR) in 4 (8 %) patients; partial response (PR) in 26 (53 %) patients; minimal response (MR) in 2 (4 %) patients; stable disease (SD) in 8 (16.3 %) patients, and progressive disease (PD) in 8 (16.3 %) patients. The objective response rate, including CR+VGPR+PR, was obtained in 31 (63.1 %) patients. The objective response rate, including MR, was seen in 33 (67.1 %) patients. Hematological and non-hematological toxicities were moderate. Taking into account the above, the RVP therapeutic regimen has demonstrated its efficacy as a second-line therapy for MM, and its clinical use can solve the problem of relapsed/refractory to bortezomib-based regimens MM management.

About the Authors

T. A. Мitinа
V.F. Vladimirskiy Moscow Regional Research and Clinical Institute
Russian Federation
61/2 Shchepkina St., Moscow, 129110


A. K. Golenkov
V.F. Vladimirskiy Moscow Regional Research and Clinical Institute
Russian Federation
61/2 Shchepkina St., Moscow, 129110


E. V. Trifonova
V.F. Vladimirskiy Moscow Regional Research and Clinical Institute
Russian Federation
61/2 Shchepkina St., Moscow, 129110


E. V. Kataeva
V.F. Vladimirskiy Moscow Regional Research and Clinical Institute
Russian Federation
61/2 Shchepkina St., Moscow, 129110


L. L. Vysotskaya
V.F. Vladimirskiy Moscow Regional Research and Clinical Institute
Russian Federation
61/2 Shchepkina St., Moscow, 129110


Yu. B. Chernykh
V.F. Vladimirskiy Moscow Regional Research and Clinical Institute
Russian Federation
61/2 Shchepkina St., Moscow, 129110


S. G. Zakharov
V.F. Vladimirskiy Moscow Regional Research and Clinical Institute
Russian Federation
61/2 Shchepkina St., Moscow, 129110


K. A. Belousov
V.F. Vladimirskiy Moscow Regional Research and Clinical Institute
Russian Federation
61/2 Shchepkina St., Moscow, 129110


A. V. Karaulov
I.M. Sechenov First Moscow State Medical University
Russian Federation
8 Build. 2 Trubetskaya St., Moscow, 119991


References

1. Митина Т.А., Голенков А.К., Катаева Е.В. и др. Эффективность бортезомиба и бортезомибсодержащих программ лечения больных рецидивирующей и резистентной множественной миеломой. Терапевтический архив 2010;82(7):57–61. [Mitina T.A., Golenkov A.K., Kataeva E.V. et al. The efficacy of bortezomib and bortezomib-containing treatment for patients with relapsed and refractory multiple myeloma. Terapevticheskiy arkhive = Therapeutic Archives 2010;82(7):57–61. (In Russ.)].

2. Голенков А.К., Барышников А.Ю., Караулов А.В., Митина Т.А. Лечение множественной миеломы. М., 2009. [Golenkov A.K., Baryshnikov A.Yu., Karaulov A.V., Mitina T.A. Treatment of multiple myeloma. Moscow, 2009. (In Russ.)].

3. Митина Т.А., Голенков А.К., Трифонова Е.В. и др. Эффективность бортезомиба, мелфалана и преднизолона (ВМП) у пациентов с впервые выявленной множественной миеломой. Medline.ru 2013;14:1030–50. [Mitina T.A., Golenkov A.K., Trifonova E.V. et al. The efficacy of bortezomib, melphalan and prednisone (VMP) in patients with newly diagnosed multiple myeloma. Medline.ru 2013;14:1030–50. (In Russ.)].

4. Richardson P.G., Wanling X., Sundar J. et al. A phase 2 trial of lenalidomide, bortezomib, and dexamethasone in patient with relapsed and relapsed/refractory myeloma. Blood 2014;123(10):1461–8.

5. Бессмельцев С.С., Карягина Е.В., Стельмашенко Л.В. и др. Эффективность леналидомида при рефрактерных/резистентных формах множественной миеломы. Онкогематология 2012;(1):6–14. [Bessmel,tsev S.S., Karyagina E.V., Stel,mashenko L.V. et al. The efficacy of lenalidomide in refractory/resistant multiple myeloma. Onkogematologiya = Oncohematology 2012;(1):6–14. (In Russ.)].

6. Mitsiades N., Mitsiades C.P., Poulaki V. et al. Apoptotic signaling induced by immunomodulatory thalidomide analogs in human multiple myeloma cells: therapeutic implications. Blood 2002;99(12):4525–30.

7. Hideshima T., Richardson P., Chauhan D. et al. The proteasome inhibitor PS-341 inhibits growth, induces apoptosis, and overcomes drug resistance in human multiple myeloma cells. Cancer Res 2001;61(7):3071–6.

8. Moreau P., Avet-Loiseau H., Facon T. et al. Bortezomib plus dexamethasone versus reduced-dose bortezomib, thalidomide plus dexamethasone as induction treatment before autologous stem cell transplantation in newly diagnosed multiple myeloma. Blood 2011;118(22):5752–8.

9. Harousseau J.L., Attal M., Avet-Loiseau H. et al. Bortezomib plus dexamethasone is superior to vincristine plus doxorubicin plus dexamethasone as induction prior to autologous stem cell transplantation in newly diagnosed multiple myeloma: results of the IFM 2005-01 phase III trial. J Clin Oncol 2010;28(30):4621–9.

10. Jakubowiak A.J., Griffith K.A., Reece D.E. et al. Lenalidomide, bortezomib, pegylated liposomal doxorubicin, and dexamethasone in newly diagnosed multiple myeloma: a phase 1/2 Multiple Myeloma Research Consorcium trial. Blood 2011;118(3):535–43.

11. Rajkumar S.V., Jacobus S., Callander N.S. et al. Lenalidomide plus high-dose dexamethasone versus lenalidomide plus lowdose dexamethasone as initial therapy for newly diagnosed multiple myeloma: an open label randomized controlled trial. Lancet Oncol 2010;11(1):29–37.

12. Richardson P.G., Weller E., Lonial S. et al. Lenalidomide, bortezomib, and dexamethasone combination therapy in patients with newly diagnosed multiple myeloma. Blood 2010;116(5):679–86.

13. Zonder J.A., Crowley J., Hussein M.A. et al. Lenalidomide and high-dose dexamethasone compared with dexamethasone as initial therapy for multiple myeloma: a randomized Southwest Oncology Group trial (S 0232). Blood 2010;116(26):5838–41.

14. Cavo M., Tacchetti P., Patriarca F. et al. Bortezomib with thalidomide plus dexamethasone compared with thalidomide plus dexamethasone as induction therapy before, and consolidation therapy after, double autologous stem-cell transplantation in newly diagnosedmultiple myeloma: a randomised phase 3 study. Lancet 2010;376(9758):2075–85.

15. Garderet L., Iacobelli S., Moreau P. et al. Superiority of the triple combination of bortezomib-thalidomide-dexamethasone over the dual combination thalidomidedexamethasone in patients with multiple myeloma progressing or relapsing after autologous transplantation: the MMVAR/IFM 2005–04 Randomized Phase III Trial from chonic Leukemia Working Party of European Group for Blood and Marrow Transplantation. J Clin Oncol 2012;30(20):2475–82.

16. Rosinol L., Orio A., Teruel A. et al. Superiority of bortezomib, thalidomide, and dexamethasone (VTD) as induction pretransplantation therapy in multiple myeloma: a randomized phase 3 PETHEMA/GEM study. Blood 2012;120(8):1589–96.

17. Wang A., Duan Q., Liu X. et al. Bortezomib plus lenalidomide/thalidomide vs bortezomib or lenalidomide/thalidomide – contaning regimens as induction therapy in newly diagnosed multiple myeloma: metaanalysis of randomized controlled trials. Ann Hematol 2010;91(11):1779–84.

18. Митина Т.А., Голенков А.К., Яздовский В.В. и др. Кинетика свободных легких цепей иммуноглобулинов сыворотки крови у пациентов с множественной миеломой в процессе проведения курсов химиотерапии, включающих леналидомид. Иммунология 2014;35(6):29–33. [Mitina T.A., Golenkov A.K., Yazdovskiy V.V. et al. Kinetics of serum free immunoglobulin light chains in patients with multiple myeloma during chemotherapy, including lenalidomide. Immunologiya = Immunology 2014;35(6):29–33. (In Russ.)].

19. Bradwell A.R., Carr-Smith H.D., Mead G.P. et al. Serum test for assessment of patients with Bence Jones myeloma. Lancet 2003;361(9356):489–91.

20. Durie B.G., Harousseau J.L., Miguel J. et al. International uniform response criteria for multiple myeloma. Leukemia 2006;20(9):1467–73.

21. Kumar S., Flinn I., Richardson P.G. et al. Randomized, multicenter, phase 2 study (EVOLUTION) of combinations of bortezomib, dexamethasone, cyclophosphamide, and pegylated liposomal doxorubicin, and dexamethasone in newly diagnosed multiple myeloma. Blood 2011;118(3):543–5.

22. Offidani M., Corvatta L., Polloni C. et al. Talidomide, dexamethasone, Doxil and Velcade (ThaDD-V) followed by consolidation/maintenance therapy in patients with relapsed/refractory multiple myeloma. Ann Hematol 2011;90(12): 1449–56.

23. Ludwig H., Viterbo L., Greil R. et al. Randomized phase II study of bortezomib, thalidomide, and dexamethasone with or without cyclophosphamide as induction therapy in previously untreated multiple myeloma. J Clin Oncol 2013;31(2): 247–55.


Review

For citations:


Мitinа T.A., Golenkov A.K., Trifonova E.V., Kataeva E.V., Vysotskaya L.L., Chernykh Yu.B., Zakharov S.G., Belousov K.A., Karaulov A.V. Efficacy of lenalidomide, bortezomib, and prednisolone in patients with relapsed or refractory multiple myeloma. Oncohematology. 2015;10(4):8-14. (In Russ.) https://doi.org/10.17650/1818-8346-2015-10-4-8-14

Views: 12073


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 1818-8346 (Print)
ISSN 2413-4023 (Online)