ReviewsAugmenting Autologous Stem Cell Transplantation to Improve Outcomes in Myeloma

- Myeloma outcomes have improved with new agents, but autologous stem cell transplantation remains the standard of care
- Bortezomib, melfufen, and targeted irradiation in conditioning merit phase III trials
- Novel agent consolidation achieves high rates of minimal residual disease negativity in phase II studies
- New antibodies, kinase inhibitors, and T cell therapies may augment immune response
- Minimal residual disease, sustained complete response, and positron emission tomography negativity should be considered as surrogate endpoints in clinical trials

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.

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