Early mortality after autologous hematopoietic stem cell transplantation (ASCT) for light-chain amyloidosis has declined dramatically in recent years, and 5-year survival is now deemed “excellent” at 77%, according to a report published online Sept. 14 in Journal of Clinical Oncology.
Light-chain amyloidosis results in deposition of insoluble amyloid fibers in many tissues, particularly the heart and kidneys, and can lead to organ failure and death. While medical therapies target the plasma cell clone that is the source of the amyloid, treatments have minimal effect on amyloid that has already accumulated in tissues. Alternatively, ASCT can produce durable hematologic responses and has resulted in improved function of affected organs, based on several single-center studies.
However, the only large, prospective randomized clinical trial to compare ASCT and medical therapy was done in 2007. That study showed autotransplantation carried a high (24%) early mortality, which contributed heavily to inferior overall survival, said Dr. Anita D’Souza of the division of hematology and oncology, Medical College of Wisconsin, Milwaukee, and her associates.
Since that study, supportive care during the peritransplantation period has greatly improved. Large U.S. transplant centers now report that early mortality is less than 5%.
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To assess time trends in autotransplantation mortality, Dr. D’Souza and her associates analyzed data from the Center for International Blood & Marrow Transplant Research, a registry that collects transplant data from 320 centers worldwide and captures information concerning most U.S. procedures. They focused on 1,536 North American patients with light-chain amyloidosis who underwent ASCT during three successive 5-year periods: 1995-2000, 2001-2006, and 2007-2012. The median follow-up was 56 months.
Over time, 30-day mortality declined from 11% to 5% to 3%, respectively; and 100-day mortality declined from 20% to 11% to 5%. One-year overall survival rose from 75% to 85% to 90%, and 5-year overall survival improved from 55% to 61% to 77%.
Even among patients with renal amyloidosis, 3-year overall survival improved over time from 78% during the earliest study period to 89% during the most recent time period. However, mortality did not improve significantly over time among patients with cardiac involvement, which continues to be the single most-important variable associated with poor outcomes, the researchers said (J Clin Oncol. 2015 Sep 14 [doi:10.1200/JCO.2015.62.4015]).
A transplant center’s experience with this procedure proved to be of crucial importance to early patient mortality. Centers that performed a low volume of ASCT for light-chain amyloidosis, defined as fewer than four transplants per year, had a 30-day mortality of 5% and a 100-day mortality of 7%, while centers that performed more than four procedures per year had significantly lower mortalities of 1% and 3%, respectively. There were no significant differences between low- and high-volume centers regarding patient, organ, or medication factors, which “led us to believe that high-volume centers do not necessarily select fitter patients for transplantation. Rather, they may be more experienced in supporting and treating these patients in the early posttransplantation period,” Dr. D’Souza and her associates said.
These “reassuring” findings, together with the recent development of novel plasma-cell–targeting agents such as bortezomib, suggest that it is time to consider performing a more current multicenter prospective study comparing autotransplantation against medical therapy, they added.