Expert perspective: Highlights on myeloma cell therapy from the American Society of Hematology Annual Meeting 2019

Abstract

The use of high dose melphalan with stem cell rescue (ASCT) has been part of the standard of care for myeloma (MM) patients since the 1990s. Recent data from the European Group for Blood and Marrow Transplantation (EBMT) were presented, which included 103 032 patients from 54 countries from 1993 to 2017. This showed an increasing number of patients receiving ASCT and longer progression-free survival (PFS) and overall survival (OS) overtime along with increased use of novel agents and triple-therapy initially. 1 Fortunately, nine agents have been approved for the treatment of MM by regulatory agencies from 2003 to 2019 with resulting improvement in clinical outcomes. Despite this improvement, the majority of MM patients continue to relapse. New cell therapy options, including chimeric antigen receptor (CAR)-T-cell therapies, are being explored in heavily pretreated and high-risk/early relapse patients. 2 In this commentary, we highlight studies presented at the American Society of Hematology (ASH) Annual Meeting held in Orlando, FL in December 2019. 2 | HI G H DOS E MELPHAL AN AND S TEM CELL RE SCUE IN MYELOMA 2.1 | Does ASCT remain relevant in the treatment of multiple myeloma? Upfront ASCT has been associated in a phase III study with deep response, MRD negativity and longer PFS when compared to delayed ASCT. Despite this, OS has been similar in upfront vs delayed transplant using novel agents as initial therapy. 3 The FORTE study in newly diagnosed myeloma (NDMM) compared four cycles of carfilzomib/lenalidomide/dexamethasone (KRd) followed by ASCT versus 12 cycles of KRd without ASCT both showing similar rates of MRD negativity. Despite similar MRD negativity, patients that received ASCT relapsed less compared to patients without ASCT, particularly in patients with Revised International Staging System (R-ISS) II/III. 4 Another study of 124 NDMM patients (93 had upfront and 31 delayed ASCT) showed similarly that upfront ASCT provided significantly better PFS1 (from diagnosis to 1st relapse, PFS1 = 6.45 vs 1.25 years, P < .001) and PFS2 (from diagnosis to 2nd relapse, PFS2 = 9.19 vs 3.69 years, P < .001). 5 2.2 | What are the factors that may predict early relapse after ASCT? Disease relapse is an obstacle to long-term survival in MM patients. The analysis of 474 NDMM patients from the FORTE study identified three factors that can predict early disease relapse at 18 months. These factors include: R-ISS II/III (particularly those patients with high LDH level), presence of circulating plasma cells and MRD status prior to ASCT. 6 The Center for International Blood and Marrow Transplant Research (CIBMTR) has generated a model to predict relapsed disease in patients treated with upfront ASCT. 7 The model included cytogenetic risk, initial therapy, bone marrow plasma cell infiltration prior to ASCT and number