Current and Future Roles of Autologous Stem Cell Transplantation in Multiple Myeloma
Autologous stem cell transplantation is the standard of care and can significantly improve clinical outcomes for transplant-eligible patients with multiple myeloma. However, relapses still occur, so there is great interest in optimizing the paradigm, drawing on additional tools.
Edward W. and Betty Knight Scripps Professor of Medicine
“Unfortunately, even after early transplantation, it appears that relapse might be inevitable, so we are seeking ways to improve on this paradigm. Looking to the future, the early use of CAR T-cell therapy and other types of immunotherapy might be one way to achieve this.”
Induction therapy followed by autologous stem cell transplantation and maintenance is the standard of care for eligible patients with multiple myeloma. There is no strict age barrier to autologous stem cell transplant eligibility. We take multiple factors into account, and an age of 65 or 70 years, for example, does not have to be a hard cutoff for transplant.
High-risk patients do gain benefit from early transplant. Delayed transplantation after early stem cell collection and storage may be appropriate in some circumstances as well. When counseling patients on the timing, we explain that there are many reasons to prefer early transplantation, if one is willing and able. One of those reasons is that delayed transplant is not always feasible later on; sometimes things interfere with the ability to undergo transplant at relapse. But we also recognize that delayed transplantation may be preferable for personal reasons, including any number of important life concerns, family and work issues, or caregiver-related concerns. And, in standard-risk patients, the overall survival with early transplantation seems to be identical to delayed transplantation.
Unfortunately, even after early transplantation, it appears that relapse might be inevitable, so we are seeking ways to improve on this paradigm. Looking to the future, the early use of chimeric antigen receptor (CAR) T-cell therapy and other types of immunotherapy might be one way to achieve this. CAR T-cell therapy immediately following transplant instead of maintenance therapy is one possibility. This would provide an immunotherapy component right after transplant, as well as long-term remission with a nice treatment-free interval. Using just CAR T-cell therapy instead of the transplant could also be considered. CAR T-cell therapy is associated with less toxicity than transplant, and the transplant may still be an option later on. These are just some potential strategies that we will have to study in clinical trials, but, clearly, early CAR T-cell therapy is under investigation, and we will be following those studies with interest.
Similarly, the use of bispecific antibodies, either in the induction regimen or as consolidation right after the transplantation, or as post-transplant maintenance, seems promising. The goal with novel induction regimens is to induce a very deep response so that the graft is not contaminated at all or is contaminated as little as possible. Other innovative approaches include trying to achieve better efficacy at the time of conditioning (eg, perhaps adding something to melphalan).
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