The Future of Post-Autologous Stem Cell Transplant Therapy for Multiple Myeloma

Review Article

Ann Hematol Oncol. 2015; 2(9): 1061.

The Future of Post-Autologous Stem Cell Transplant Therapy for Multiple Myeloma

Holstein SA, Ho CM, Balderman SR and McCarthy PL*

Department of Medicine, Roswell Park Cancer Institute, USA

*Corresponding author: McCarthy PL, Department of Medicine, Roswell Park Cancer Institute, Elm and Carlton Sts, Buffalo, NY 14251, USA

Received: August 24, 2015; Accepted: November 11, 2015; Published: November 15, 2015

Abstract

Multiple myeloma is a plasma cell malignancy characterized by lytic bone disease, monoclonal protein production, and immune dysregulation. For patients eligible for high-dose chemotherapy, the standard of care has been induction therapy with immunomodulatory drugs and/or proteasome inhibitorbased therapy followed by autologous stem cell transplant (ASCT). Despite this approach, nearly all patients eventually relapse and there has therefore been interest in the use of post-ASCT maintenance therapy to prolong disease control and improve survival. Phase III randomized studies have demonstrated that lenalidomide post-ASCT results in improved outcomes. There are less robust data available for the use of bortezomib. Here we review the current literature as well as the ongoing clinical trials pertaining to the use of post-ASCT maintenance therapies for myeloma. We also discuss a variety of novel therapeutic strategies; including monoclonal antibodies, immune checkpoint blockade, and CAR-T cell therapy, which may represent the future of post-ASCT therapy.

Keywords: Multiple myeloma; Autologous stem cell transplant; Maintenance; Consolidation; Minimal residual disease

Abbreviations

ALL: Acute Lymphoblastic Leukemia; AML: Acute Myeloid Leukemia; ASCT: Autologous Stem Cell Transplant; ASO PCR: Allele-Specific Oligonucleotide PCR; BET: Bromodomain and Extra- Terminal; BiTE: Bispecific T cell Engagers; CAR: Chimeric Antigen Receptor; CIR: Cumulative Incidence Risk; CR: Complete Response; DCEP: Dexamethasone/Cyclophosphamide/Etoposide/Cisplatin; IMiD: Immunomodulatory Drug; MDS: Myelodysplastic Syndrome; MFC: Multiparametric Flow Cytometry; MPR: Melphalan/ Prednisone/Lenalidomide; MRD: Minimal Residual Disease; PI: Proteasome Inhibitor; OS: Overall Survival; PD-1: Programmed cell Death protein 1; PD-L1: Programmed Death Ligand 1; PFS: Progression Free Survival; RVD: Lenalidomide/Bortezomib/ Dexamethasone; SPM: Second Primary Malignancy; TTP: Time To Progression; HTS: High-throughput Sequencing; VGPR: Very Good Partial Response.

Introduction

The outcomes of patients with multiple myeloma have markedly improved with the introduction of immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs). Induction therapy consisting of IMiD- and/or PI-based therapy followed by consolidation with high dose melphalan and autologous stem cell transplantation (ASCT) remains a standard of care for younger patients. However, as nearly all patients relapse following ASCT there has been continued interest in the use of post-ASCT therapies to delay disease recurrence and prolong overall survival (OS). One approach has been further consolidation post-ASCT followed by no further treatment or by maintenance therapy. Another approach has been initiation of maintenance therapy after a period of recovery following ASCT. Earlier studies concentrated on first interferon and then thalidomide (with or without corticosteroids) as maintenance therapy. However, prolonged use of these agents was limited by side effects and studies did not show a consistent improvement in OS. More recent studies have focused on lenalidomide and bortezomib. Here we review these studies and discuss how novel agents might become incorporated into post-ASCT therapy.

Lenalidomide maintenance

Palumbo et al. performed the first study to incorporate lenalidomide in the post-ASCT setting. In this phase II study, patients underwent induction therapy with bortezomib, doxorubicin, and dexamethasone followed by tandem ASCT (melphalan 100 mg/m2) [1]. The post-ASCT therapy consisted of four cycles of lenalidomide plus prednisone followed by lenalidomide alone continued until disease relapse. The most frequent grade 3/4 adverse events included neutropenia, thrombocytopenia and pneumonia. Subsequently three randomized studies involving lenalidomide maintenance have been performed (Table 1).