#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Lenalidomide Maintenance Therapy in Patients with Multiple Myeloma


Authors: Ľ. Roziaková 1;  M. Mistrík 2
Authors place of work: Oddelenie klinickej patofyziológie, Klinika hematológie a transfuziológie LF UK a UN Bratislava 1;  Klinika hematológie a transfuziológie LF UK a UN Bratislava 2
Published in the journal: Klin Onkol 2013; 26(3): 186-190
Category: Review

Summary

Maintenance therapy was recently defined as any treatment administered after the completion of induction therapy in patients whose disease is either responsive or nonprogressive at the time, with the goal of prolonging survival. Several studies have evaluated the use of novel agents as part of posttransplantation maintenance to improve progression free survival and overall survival. As shown by recent clinical trials, thalidomide and bortezomib are more indicated as consolidation agents, increasing the response rates. In contrast, lenalidomide showed a low toxicity profile and a benefit from prolonged treatment, making the drug one of the best choices for maintenance treatment. The role of lenalidomide in the maintenance therapy was evaluated in three randomized clinical trials. Lenalidomide was associated with a significantly increased progression free survival and in one study with a significant survival benefit. An unexpected finding from these trials was a modest increase in the incidence of secondary cancers. Whether lenalidomide maintenance should be routinely offered to patients is controversial among experts. For now, lenalidomide maintenance should be considered standard for patients not achieving a complete remission after stem cell transplantation, and for high‑risk patients. For patients with low‑ risk disease, the risk/ benefits of lenalidomide maintenance versus watchful waiting should be discussed until we have more data regarding survival benefits. Further analysis of lenalidomide maintenance therapy to determine the long‑term risk of secondary malignancies and longer follow‑up to assess the impact on overall survival is required.

Key words:
multiple myeloma –  lenalidomide –  maintenance


Zdroje

1. Hájek R, Krejčí M, Pour L et al. Multiple Myeloma. Klin Onkol 2011; 24 (Suppl): S10– S13.

2. Hájek R, Zahradová L. Možnosti a limitace farmakoterapie mnohopočetného myelomu. Farmakoterapie 2012; 3: 25– 28.

3. Ludwig H, Durie BG, McCarthy P et al. IMWG consensus on maintenance therapy in multiple myeloma. Blood 2012; 119(13): 3003– 3015.

4. Badros AZ. The role of maintenance therapy in the treatment of multiple myeloma. J Natl Compr Center Netw 2010; 8 (Suppl 1): S21– S27.

5. Alexanian R, Balcerzak S, Haut A et al. Remission maintenance therapy for multiple myeloma. Arch Intern Med 1975; 135(1): 147– 152.

6. Belch A, Shelley W, Bergsagel D et al. A randomized trial of maintenance versus no maintenance melphalan and prednisone in responding multiple myeloma patients. Br J Cancer 1988; 57(1): 94– 99.

7. Fritz E, Ludwig H. Interferon‑alpha treatment in multiple myeloma: meta‑analysis of 30 randomized trials among 3948 patients. Ann Oncol 2000; 11(11): 1427– 1436.

8. Sonneveld P, Schmidt‑ Wolf IG, van der Holt B et al. Bortezomib induction and maintenance treament in patients with newly diagnosed multiple myeloma: results of the randomized phase III HOVON‑ 65/ CMMG‑ HD4 trial. J Clin Oncol 2012; 30(24): 2946– 2955.

9. Attal M, Harousseau JL, Leyvraz S et al. Maintenance therapy with thalidomide improves survival in patients with multiple myeloma. Blood 2006; 108(10): 3289– 3294.

10. Spencer A, Prince HM, Roberts AW et al. Consolidation therapy with low‑dose thalidomid and prednisolone prolongs the survival of multiple myeloma patients undergoing a single autologous stem‑ cell transplantation procedure. J Clin Oncol 2009; 27(11): 1788– 1793.

11. Barlogie B, Pineda‑ Roman M, van Rhee F et al. Thalidomide arm of total therapy 2 improves complete remission duration and survival in myeloma patients with metaphase cytogenetic abnormalities. Blood 2008; 112(8): 3115– 3121.

12. Lokhorst HM, van der Holt B, Zweegman S et al. A randomized phase 3 study on the effect of thalidomide combined with adriamycin, dexamethasone, and high‑dose melphalan, followed by thalidomide maintenance in patients with multiple myeloma. Blood 2010; 115(6): 1113– 1120.

13. Morgan GJ, Gregory WM, Davies FE et al. The role of maintenance thalidomide therapy in multiple myeloma: MRC Myeloma IX results and meta‑analysis. Blood 2012; 119(1): 7– 15.

14. Krishnan A, Pasquinin MC, Logan B et al. Autologous hematopietic stem‑ cell transplantation followed by allogeneic or autologous hematopoietic stem‑ cell transplantation in patients with multiple myeloma (BMT CTN 0102): a phase 3 bio­logical assignment trial. Lancet Oncol 2011; 12(13): 1195– 1203.

15. Cives M, Simone V, Brunetti O et al. Novel lenalidomide‑based combinations for treatment of multiple myeloma. Crit Rev Oncol Hematol 2013; 85(1): 9– 20.

16. Holánek M, Hájek R. The use of lenalidomide in the treatment of multiple myeloma. Klin Onkol 2010; 23(2): 67– 72.

17. Gandhi AK, Kang J, Capone L et al. Dexamethasone synergizes with lenalidomide to inhibit multiple myeloma tumor growth, but reduces lenalidomide‑induced immunomodulation of T and NK cell function. Curr Cancer Drug Targets 2010; 10(2): 155– 167.

18. Cives M, Milano A, Dammacco F et al. Lenalidomide in multiple myeloma: current experimental and clinical data. Eur J Haematol 2012; 88(4): 279– 291.

19. Lupo B, Palumbo A. Lenalidomide in the treatment of young patients with multiple myeloma: from induction to consolidation/ maintenance therapy. Adv Hematol. In press 2012.

20. Attal M, Lauwers‑ Cances V, Marit G et al. Lenalidomide maintenance after stem‑ cell transplantation for multiple myeloma. N Engl J Med 2012; 366(19): 1782– 1791.

21. McCarthy PL, Owzar K, Hofmeister CC et al. Lenalidomide after stem‑ cell transplantation for multiple myeloma. N Engl J Med 2012; 366(19): 1770– 1781.

22. Palumbo A, Hajek R, Delforge M et al. Continuous lenalidomide treatment for newly diagnosed multiple myeloma. N Engl J Med 2012; 366(19): 1759– 1769.

23. Falco P, Cavallo F, Larocca A et al. Lenalidomide‑ prednisone induction followed by lenalidomide‑ melphalan‑ prednisone consolidation and lenalidomide‑ prednisone maintenance in newly diagnosed elderly unfit myeloma patients. Leukemia. In press 2012.

24. Palumbo A, Gay F, Falco P et al. Bortezomib as induction before autologous transplantation, followed by lenelidomide as consolidation‑ maintenance in untreated multiple myeloma patients. J Clin Oncol 2010; 28(5): 800– 807.

25. Roussel M, Avet‑ Loiseau H, Moreau P et al. Frontline therapy with bortezomib, lenalidomide, and dexamethasone (VRD) induction followed by autologous stem cell transplantation, VRD consolidation and lenalidomide maintenance in newly diagnosed multiple myeloma patients: primary results of the IFM 2008 Phase II Study. Blood 2010; 116(21): 274– 275.

26. Kneppers E, van der Holt B, Kersten MJ et al. Lenalidomide maintenance after nonmyeloablative allogeneic stem‑ cell transplantation in multiple myeloma is not feasible: results of the HOVON 76 Trial. Blood 2011; 118(9): 2413– 2419.

27. Dimopoulos MA, Richardson PG, Brandenburg N et al. A review of second primary malignancy in patients with relapsed or refractory multiple myeloma treated with lenalidomide. Blood 2012; 119(12): 2764– 2767.

28. Giralt S, Stadtmauer E, McCarthy P. What did we learn in 2010 from the phase III trials? Is maintenance therapy the new standard for myeloma? Biol Blood Marrow Transplant 2011; 17 (Suppl 1): S30– S32.

Štítky
Paediatric clinical oncology Surgery Clinical oncology

Článok vyšiel v časopise

Clinical Oncology

Číslo 3

2013 Číslo 3
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Prihlásenie
Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa

#ADS_BOTTOM_SCRIPTS#