EMBT 2018 | Therapies for fit, elderly MM patients

The MM Hub attended the 44th Annual Meeting of the European Society for Blood and Marrow Transplantation held in Lisbon, Portugal, from 18–21 March 2018. On Sunday 18 March 2018 an Intergroupe Francophone du Myélome (IFM Group) non-profit symposium was held entitled Multiple Myeloma in 2018: the IFM global perspective. The session was moderated by Mohamad Mohty, from the Hospital Saint-Antoine and University Pierre & Marie Curie, Paris, France and Jean Luc Harousseau, from the University of Nantes, France. The second talk, presented by Thierry Facon, from Service des Maladies du Sang, Hôpital Claude Huriez, Lille, France, answered the question: What is new in the therapy for fit, elderly MM patients?

Professor Facon began his talk by presenting a case study of a 75 year-old fit and elderly patient, and the results from a survey in which physicians had shared the treatment regimens they would use for this patient. The most popular treatments included bortezomib, melphalan, prednisolone (VMP; 32%), bortezomib, lenalidomide, dexamethasone (VRD; 23%) and induction therapy followed by autologous stem cell transplantation (ASCT) and consolidation (24%). Using the international myeloma working group (IMWG) frailty score proposed by Palumbo et al, multiple myeloma (MM) patients are now stratified into three categories with different recommendations for treatment regimens and dosage (Table 1). However, Professor Facon explained it can be difficult to categorize all patients using these criteria.

Table 1. Stratification of patients using the IMWG frailty score (modified from Palumbo et al.)

Professor Facon then briefly described the Eastern Cooperative Oncology Group (ECOG) study which categorized elderly MM patients into frail and non-frail, and revealed a 10-month improvement in overall survival (OS) at 12-months in the non-frail category, as well as a 12-month improvement in progression free survival (PFS) at 18 months.

The SWOG SO777 clinical trial showed the superiority of bortezomib, lenalidomide, and dexamethasone (VRD) over lenalidomide and dexamethasone alone (Rd), in elderly and fit MM patients, with a 13-month increase in PFS and an 11-month increase in OS, in the VRD treatment arm.

Country-wide differences in treatments for fit and elderly MM patients were briefly mentioned. For example, in Spain, patients under the age of 65 are now no longer offered a transplant, as the decision was made that promising triplet and quadruplet drug regimens should replace this option. Professor Facon said he was unsure if this was good or bad, as transplant is still the standard of care (SOC) for patients under the age of 65 in many other countries. The design of the Spanish GEMFIT2016 study led by Maria-Victoria Mateos, was then described in which treatment of fit, elderly MM patients excludes the use of transplant. Newly diagnosed MM patients (N = 462) have been divided into three arms to receive either: 1) induction with VMP, 2a) carfilzomib, lenalidomide, dexamethasone (KRd) induction, or 2b) KRd-Daratumumab (Dara) induction. All arms were then given consolidation with RdDara, and then either no maintenance or maintenance with daratumumab plus lenalidomide, with the endpoint being immunophenotypic complete response.

In most countries, ASCT remains a standard of care for patients ≤65 years of age, based largely on data from the IFM 2009 study and EMN studies. No large phase III randomized studies have established the role of ASCT in elderly and fit MM patients in the era of novel agents. Additionally, it has been found that ASCT (single and double transplant) seems to be routinely performed in some countries for elderly, fit MM patients between the age of 65 and 75.

Data from the IFM 99-06 study, in which elderly NDMM patients were assigned to three different treatment arms to receive melphalan and prednisone (MP); melphalan, prednisolone and thalidomide (MP-T) and MEL100 which included ASCT, was described. However, the use of transplant in this patient population was found to be detrimental. The German DSMM XIII study, also found that the risk of transplant for elderly patients may outweigh the benefit, which appears to be a general theme for patients in the 70–75 age category.

Professor Facon emphasized the relevance of assessing fitness and frailty for optimal treatment selection and explained that the results from various clinical studies have shown that elderly patients assessed as being ‘fit’ can tolerate more aggressive treatments, including triplet or quadruplet drug combinations. Finally, Professor Facon stated that a subset of fit elderly patients might be good candidates for high-dose melphalan followed by ASCT, and that the future of ASCT in this era of novel agents and combination regimens, seems uncertain.