Multiple myeloma treatment at relapse after autologous stem cell transplantation: A practical analysis

Abstract

Over the past decade, significant advances have been made in the field of multiple myeloma. Introduction of the so-called novel agents, proteasome inhibitors (PI) and immunomodulatory drugs (IMiD), and improved supportive care have resulted in significantly better outcome. Standard first line treatment in fit patients include PI and IMiD based induction, high dose melphalan with autologous hematopoietic stem cell transplantation (ASCT) and consolidation/maintenance. However, despite these progresses MM remains incurable for the majority of patients and most patients will relapse. Next generation PI (carfilzomib, ixazomib) and IMiD (pomalidomide) and new therapeutic classes: monoclonal antibody (elotuzumab, daratumumab) and pan-deacetylase inhibitors (panobinostat) have been successfully evaluated in relapse multiple myeloma. Some of these new agents are now approved for multiple myeloma treatment at relapse. However choosing the most appropriate treatment at relapse may be difficult. This review sum up the most important studies and provide evidence to choose the most relevant therapeutic strategy for relapse after ASCT, based on disease, patient and previous treatment related parameters.

Autologous Stem Cell Transplantation in Multiple Myeloma in the Era of Novel Drug Induction: A Retrospective Single-Center Analysis

“…This is also in agreement with several other trials [7,8,9] and underlines the urgent medical need for further research on drugs affecting additional targets. Novel compounds such as the immunomodulatory drug pomalidomide, the next-generation proteasome inhibitors carfilzomib and ixazomib, panobinostat, a pan-histone deacetylase inhibitor, and the monoclonal antibodies elotuzumab and daratumumab already show promising results in the treatment of myeloma patients [44,45,46,47,48,49]. …”

Hematopoietic Stem Cell Transplantation in Multiple Myeloma in the Era of Novel Therapies

“…There is no standard of care for MM relapse after autologous HSCT [183,184]. Regimens that are composed of combination therapy with (1) drugs having synergistic effect and no crossresistance and (2) one or two novel therapies are generally preferred as they lead to deeper and longer responses that are translated into improved survival [16,[183][184][185]. However, treatment should be individualized based on toxicity as well as patient and disease characteristics [184].…”

How I treat first relapse of myeloma

“…When the relapse is symptomatic, treatment should be rapid to relieve symptoms and to avoid end-organ damage. 37,39 In this case, the patient had a biochemical relapse without symptoms and usually these patients with a slow rise in the paraprotein level are managed with a stringent watchand-wait approach. The question is then when to start, if possible, before the occurrence of symptoms.…”

“…These patients require immediate treatment, usually with a triplet including 1 IMID and 1 PI. 37,39 Patients' characteristics are important for determining the benefit-to-risk ratio of a given treatment. Age and comorbidities are major factors to consider at the time of choosing relapse treatment.…”

“…22 But in the same time, new possibilities have emerged with approval by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) of no less than 6 new agents since 2012: a new IMID (pomalidomide [23][24][25][26][27] ), new PIs (carfilzomib 28,29 and ixazomib 30 ), and drugs with different modes of action like histone-deacetylase inhibitors (panobinostat 31 ) and antibodies (elotuzumab 32 and daratumumab [33][34][35] ). Reviews on the treatment of relapsed MM have been recently published [36][37][38][39] but they do not include the most recent results, especially those with daratumumab.…”