Cancer Treatment Today

Multiple myeloma is an incurable disease, and patients who respond to treatment eventually relapse and, therefore, maintenance therapy is an appealing option. While some drugs have been shown to be ineffective, others appear to be effective and which drugs and in which sequence and schedule is under active research. Maintenance must be fairly non-toxic and be able to be administered for prolonged time.

IFN use in the maintenance setting has largely been abandoned because gain in quality time was counterbalanced by serious toxicity. Use of steroids formaintenance produced a similar result.

IMiDs, PIs, and bisphosphonates are promising, but the results ahve been mixed with thalidomide. Despite its convenient route of administration (oral) and its beneficial effect on PFS, thalidomide maintenance has largely been abandoned because of its toxicity. However, lenalidomide (Revlimid, Celgene) maintenance in both the transplant and transplant-ineligible settings has shown consistent improvement in PFS and, in some studies, OS. Unfortunately, lenalidomide also has been associated with an increased risk of second primary malignancies, especially leukemia and lymphoma, but these risks are surpassed by its benefits.

Nitrogen-containing bisphosphonates, such as pamidronate and zoledronic acid, showing some benefit but whether it is due to maintenance or refection of the intial use is being studied.

The efficacy of maintenance therapy with the PI bor­tezomib (Velcade, Millennium Pharmaceuticals) is not NCCN recommended, as well as Revlmid. rThe newest drug to be studied for maintenance as well for initial therrapy is carfilzomib. Clinicaltrials. gov lists 5 studies of the combination of this drug with cytoxan and decardron, of which 4 are in the maintenance setting.

Per Sengsayadeth, S., Malard, F., Savani, B. N., Garderet, L., & Mohty, M. (2017), “Transplant-eligible patients with multiple myeloma (MM) now have extended survival after diagnosis owing to effective modern treatment strategies that include new agents in induction therapy, autologous stem cell transplant (ASCT), consolidation therapy and posttransplant maintenance therapy. Standard of care for newly diagnosed, fit patients includes ASCT and, often nowadays, posttransplant maintenance. Several large studies have shown the efficacy of maintenance with thalidomide, lenalidomide and bortezomib in the treatment scheme of MM with regards to prolonging progression-free survival and, to a lesser degree, overall survival.”    

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

Benevolo G, Larocca A, Gentile M, et al. (2011). The efficacy and safety of bortezomib and dexamethasone as a maintenance therapy in patients with advanced multiple myeloma who are responsive to salvage bortezomib-containing regimens. Cancer. 2011;117(9):1884-1890.

Food and Drug Administration (FDA). Zoledronic Acid Injection. https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/203231s011lbl.pdf

Moreau, P. et al. (2017). Multiple Myeloma: ESMO Clinical Practice Guidelines. Ann Oncol (2017) 28 (suppl 4): iv52iv61.

Sengsayadeth, S., Malard, F., Savani, B. N., Garderet, L., & Mohty, M. (2017). Posttransplant maintenance therapy in multiple myeloma: the changing landscape. Blood cancer journal, 7(3), e545.

Maiolino A, Hungria VT, Garnica M, et al; Brazilian Multiple Myeloma Study Group (BMMSG/GEMOH). Thalidomide plus dexamethasone as a maintenance therapy after autologous hematopoietic stem cell transplantation improves progression-free survival in multiple myeloma. Am J Hematol. 2012;87(10):948-952.

Stewart AK, Trudel S, Bahlis NJ, et al. A randomized phase 3 trial of thalidomide and prednisone as maintenance therapy after ASCT in patients with MM with a quality-of-life assessment: the National Cancer Institute of Canada Clinicals Trials Group Myeloma 10 Trial. Blood. 2013;121(9):1517-1523.

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.

Palumbo A, Cavallo F, Gay F, et al. Autologous transplantation and maintenance therapy in multiple myeloma. N Engl J Med. 2014;371(10):895-905.

Neville-Webbe HL, Gnant M, Coleman RE. Potential anticancer properties of bisphosphonates.Semin Oncol. 2010;37(suppl 1):S53-S65.

Palumbo A, Bringhen S, Larocca A, et al. Bortezomib-melphalan-prednisone-thalidomide followed by maintenance with bortezomib-thalidomide compared with bortezomib-melphalan-prednisone for initial treatment of multiple myeloma: updated follow-up and improved survival. J Clin Oncol. 2014;32(7):634-640.

Niesvizky R, Flinn I, Rifkin RM, et al. Efficacy and safety of three bortezomib-based induction and maintenance regimens in previously untreated, transplant-ineligible multiple myeloma (MM) patients (pts): final results from the randomized, phase 3b, US community-based UPFRONT study (NCT00507416) [ASH abstract 1966]. Blood. 2013;122(21)(suppl).

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

Rosiñol L, Oriol A, Teruel AI, et al; Programa para el Estudio y la Terapéutica de las Hemopatías Malignas/Grupo Español de Mieloma (PETHEMA/GEM) group. 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):1589-1596.

Benevolo G, Larocca A, Gentile M, et al. The efficacy and safety of bortezomib and dexamethasone as a maintenance therapy in patients with advanced multiple myeloma who are responsive to salvage bortezomib-containing regimens. Cancer. 2011;117(9):1884-1890.