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The long-term survival of people with multiple myeloma following autologous stem cell transplant has steadily improved since 1997 through with the introduction of new medicines, a large review study reports.
Older patients and those with low-risk disease show the greatest gains over time, while people with high-risk factors showed the least change, its researchers said.
The study, “Long-term outcomes after autologous stem cell transplantation for multiple myeloma,” was published in the journal Blood Advances.
An important component of multiple myeloma treatment is autologous stem cell transplantation (ASCT), which consists on using a patient’s own healthy blood stem cells to replace diseased or damaged bone marrow.
ASCT is one part of a therapy approach that also includes induction therapy (a first treatment for a disease, which in cancer often includes chemotherapy and radiation), consolidation therapy (a short course of chemotherapy after transplant), and maintenance therapy (low, long-term doses of medication to prevent disease relapse).
This approach has been consistent for decades. But as new medicines became available, they were incorporated into induction, consolidation, and maintenance treatments as standard treatments.
Treatment goals over time have also changed, with more emphasis now on delaying relapses, depleting residual malignant cells, and achieving long-term disease control — so-called “functional cures.”
To better understand how well new medicines being introduced have led to improvements in long-term survival and in functional cure among those given ASCT, researchers based at the University of Arkansas analyzed the medical records of patients newly diagnosed with myeloma its medical center and given ASCT as part of their first-line therapy.
Records covering a total of 4,329 patients, with a median age at diagnosis of 59, were reviewed. Across the entire group, these people were followed for a median of 10.5 years, and a median overall survival of 6.9 years. After three years of follow-up, almost 72% of patients had not progressed.
Patients’ were grouped patients into five time periods, based roughly on the dates they received ASCT and when clinical trials included new medicines. These periods were: 1997 or earlier (used as a reference group), 1998 to 2003, 2004 through 2008, 2009 to 2013, and 2014 or later.
Over the years, records showed that patients were diagnosed at older ages, more patients of various ethnicities (other than white) were being treated, and more patients had genetic abnormalities. More patients also participated in clinical trials as the years passed, for a total of 43% given ASCT as a first-line therapy in a study.
Compared with the reference period, patients treated at later time periods had better survival rates. And this survival rate kept improving over time, with 47% of those treated in 1997 or earlier living for five years or longer, 62% for 2004 to 2008, 61% for 2009–2013, and 70% for those treated in 2014 or later.
Overall, around 30% of patients did not survive beyond three years after a first ASCT (early mortality). But with the exception of the 2014 or later group, the rate of early mortality fell over time. Early mortality was most common in older patients, that were older, and those with chromosomal abnormalities and high genetic risk status.
Similar trends were seen in the time to disease progression or death — a measure called progression-free survival — but were more pronounced compared to overall survival.
Outcomes for both patients younger than 65 and those older improved over time, but the survival rates in the older group were consistently worse. However, after 2014 no statistical difference in five-year survival rates between older and younger patients was noted.
The steady progress in preventing myeloma-related deaths was still observed after adjusting for risk factors like age, sex, race and ethnicity, and clinical trial participation. Compared with patients treated before 1997, the mortality risk declined with each successive time period, with those treated in 2014 or later experiencing the lowest risk of death (65% lower than the reference group).
Among all patients, regardless of transplant date, a statistical analysis found that 16.4% were functionally cured of myeloma. When separated into time periods, the number of those functionally cured rose from 6.3% in 1997 or earlier, to 31.3% in 2009 through 2013. Data on those treated in 2014 or later have yet to be collected.
Patients meeting or exceeding their normal life expectancy across multiple time periods were between 10.0% and 18.6%, with no obvious trends over time.
“The results presented here are consistent with steady progress in improving outcomes for patients with MM [multiple myeloma] by the use of effective drug combinations given in conjunction with ASCT,” the scientists wrote.
“Going forward, it is clear that continued efforts to control and eradicate residual disease will be important strategies to increase the likelihood of achieving MM cure,” they added.
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