Delving Deeper to Improve Patient Care
Autologous (self) stem cell transplants (ASCT) are the backbone of current treatment regimens for multiple myeloma owing to multiple studies demonstrating their clinical benefit and positive impact on overall survival for high-risk patients. A majority of multiple myeloma patients receiving these transplants, however, will ultimately relapse. A contributing factor is likely tumor cell contamination of the collected cells (also referred to as minimal residual disease or “MRD”).
Various strategies have been tested for reducing MRD in cells collected from patients for later ASCT. At Stanford University we developed a protocol called tandem chemo-mobilization, which used two cycles of chemotherapy followed by stem cell collection, with the goal of the second collection yielding a “clean” product. In 2012 we published results showing that our method led to high-quality response rates and favorable outcomes comparable to other ASCT regimens.
Because we continually strive to improve the management of our patients and increase our understanding of treatment effectiveness, we took advantage of the recent availability of next-generation sequencing-based MRD measurement and quantification to evaluate whether the second stem cell mobilization in our protocol was actually achieving the reduction in tumor cell contamination we wanted.
In results being presented during the 2014 American Society of Hematology meeting we showed that the second cycle of chemo-mobilization not only fails to significantly reduce tumor cell contamination in the collected cells, but actually increases the frequency of myeloma cells as a fraction of the total B cells (the type of cell myeloma is derived from).
Given that tandem chemo-mobilization in patients undergoing ASCT for multiple myeloma had shown good outcomes, these results were certainly surprising. They demonstrate that no matter how many advancements we make, there’s always more to learn and more to do. We have stopped using tandem chemo-mobilization at Stanford. We’ve also started new studies looking at other ways to reduce tumor cell contamination of the stem cells collected for transplant, including the use of new agents and cell sorting techniques. And we continue to evaluate how ultra-sensitive NGS-based MRD testing of autograft samples might provide improved clinical prognostic information, complement post-transplant MRD quantification, and potentially inform treatment decisions about the timing and intensity of post-transplant maintenance therapies.
Dr. Miklos is an Assistant Professor of Medicine at Stanford University Medical Center. The views expressed here are his own and are not an endorsement of Adaptive or the clonoSEQ® Process.