Augmenting Autologous Stem Cell Transplantation to Improve Outcomes in Myeloma.
Consolidation with high-dose chemotherapy and autologous stem cell transplantation (ASCT) is the standard of care for transplantation-eligible patients with multiple myeloma, based on randomized trials showing improved progression-free survival with autologous transplantation after combination chemotherapy induction. These trials were performed before novel agents were introduced; subsequently, combinations of immunomodulatory drugs and proteasome inhibitors as induction therapy have significantly improved rates and depth of response. Ongoing randomized trials are testing whether conventional autologous transplantation continues to improve responses after novel agent induction. Although these results are awaited, it is important to review strategies for improving outcomes after ASCT. Conditioning before ASCT with higher doses of melphalan and combinations of melphalan with other agents, including radiopharmaceuticals, has been explored. Tandem ASCT, consolidation, and maintenance therapy after ASCT have been investigated in phase III trials. Experimental cellular therapies using ex vivo-primed dendritic cells, ex vivo-expanded autologous lymphocytes, Killer Immunoglobulin Receptor (KIR)-mismatched allogeneic natural killer cells, and genetically modified T cells to augment ASCT are also in phase I trials. This review summarizes these strategies and highlights the importance of exploring strategies to augment ASCT, even in the era of novel agent induction.
Department of Medicine, Oxford University Hospitals NHS Trust, United Kingdom.
Bernard
B
Maybury
Experimental Haematology, Leeds Institute of Cancer & Pathology, University of Leeds, United Kingdom.
Gordon
G
Cook
Department of Haematology, University Hospitals Birmingham NHS Foundation Trust, United Kingdom.
Guy
G
Pratt
Cancer Institute, University College London, United Kingdom.
Kwee
K
Yong
Department of Haematology, Oxford University Hospitals NHS Trust, United Kingdom; NIHR Biomedical Research Centre, Blood Theme, Oxford, United Kingdom. Electronic address: karthik.ramasamy@rdm.ox.ac.uk.
Karthik
K
Ramasamy
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods; D009101:Multiple Myeloma / Q000628:therapy*; D033581:Stem Cell Transplantation / Q000379:methods* / Q000592:standards / Q000639:trends; D019172:Transplantation Conditioning / Q000379:methods; D014182:Transplantation, Autologous / Q000379:methods* / Q000592:standards; D016896:Treatment Outcome
Conditioning; Immunotherapy; Minimal residual disease; Multiple myeloma; Stem cell transplantation