Multiple myeloma maintenance therapy: A review of the pharmacologic treatment

Abstract

Over the last decade, numerous drug therapies have emerged for the treatment of multiple myeloma including immunomodulating agents namely thalidomide, lenalidomide, and pomalidomide and proteasome inhibitors namely bortezomib and carfilzomib. These agents have transformed the treatment of multiple myeloma and the role of high-dose chemotherapy followed by stem cell transplantation in the treatment of the disease. There are now studies that evaluate the use of drug therapy as maintenance following autologous stem cell transplantation; these studies have shown improvements in surrogate endpoints such as progression-free survival. Studies that have evaluated thalidomide or lenalidomide maintenance therapy have demonstrated an overall survival (OS) benefit in individuals with multiple myeloma who received high-dose chemotherapy followed by stem cell transplantation. A meta-analysis of thalidomide maintenance therapy did show a possible late survival benefit. The use of dexamethasone, thalidomide, lenalidomide, or combination bortezomib with thalidomide in patients who did not undergo transplantation demonstrated progression-free survival benefit; although there was no OS advantage for these agents in this population. There are a number of important considerations when selecting a drug therapy strategy for maintenance therapy which includes practical considerations such as route of administration and frequency of administration. Additionally, patient-specific elements such as potential toxicities, end-organ function, quality of life, cytogenetics, and previous treatment should be considered. Additional studies are needed to elicit the timing for initiation and duration of maintenance therapy, determine the role of cytogenetics, further characterize possible resistance patterns, and determine the combinations necessary to achieve an optimal increase in OS. Until more data are available, the risks and benefits should be evaluated on a patient-specific basis when deciding to initiate maintenance therapy or observation.

Outcomes of Maintenance Therapy with Bortezomib after Autologous Stem Cell Transplantation for Patients with Multiple Myeloma

“…The selection of maintenance therapy is a major decision for physicians. Currently, we do not have conclusive guidelines regarding the use of these agents [25]. Therapy with low-dose lenalidomide is the most widely used maintenance strategy for patients with MM after transplantation.…”

Multiples Myelom – aktuelle Standards in Diagnostik und Therapie

“…In gegenwärtigen Metaanalysen und Reviewartikeln wurden neue und erfolgversprechende Therapiemöglichkeiten durch die Immunmodulatoren wie Thalidomid und Lenalidomid sowie die Proteasomeninhibitoren wie Bortezomib und Carfilzomib aufgezeigt, die ein breites Anwendungsspektrum durch die Kombinierbarkeit mit bisherigen klassischen Chemotherapeutika und Glukokortikoiden erlauben. Dies gilt nicht nur für die Erstlinientherapie, sondern insbesondere für die Rezidiv-und Konsolidierungstherapie [43].…”

“…Außerdem wird ausdrücklich auf das erhöhte Komplikationsrisiko für Thromboembolien, PNP, Infektionen und Neutropenie hingewiesen [54]. Welches medikamentös basierte Behandlungsprotokoll für die Erhaltungstherapie nach einer Stammzelltransplantation ausgewählt wird wie auch der geeignete Zeitpunkt und die Dauer hängen von vielen Variablen wie Applikationsform und -frequenz, Toxizitäten, Endorganfunktionen, Vorbehandlungen, Zytogenetik und Lebensqualität des Patienten ab [43,55,56].…”

Advances in the management of multiple myeloma

“…Tere have also been many advances in the use of maintenance therapy for MM patients. 21 Findings in earlier maintenance trials had shown an improvement in OS from continuing steroids such as single-agent oral prednisone at therapeutic doses for MM patients who had responded to initial therapy with steroids and chemotherapy. 22 Recent study fndings have suggested the beneft of other drugs as maintenance therapy for patients who completed their initial therapy.…”

“…22 Recent study fndings have suggested the beneft of other drugs as maintenance therapy for patients who completed their initial therapy. 21,[23][24][25] Specifcally, an improvement in OS with ongoing lenalidomide alone or with dexamethasone has been demonstrated in some but not all studies. [23][24][25] Unfortunately, studies with the PIs have not defned their role as maintenance drugs, 21 but the recent availability of the oral PI ixazomib will make the performance of these studies easier to undertake 7 .…”