What causes early death among patients with multiple myeloma treated with high-dose therapy followed by autologous stem cell transplantation (HDT-ASCT)?

To answer this question, Kristian Thidemann Andersen, MD, PhD, of the department of hematology at Odense University Hospital in Denmark, and colleagues investigated the outcomes of patients enrolled in the nationwide Danish Multiple Myeloma Registry, which contains information on all newly diagnosed plasma cell disorders since January 1, 2005.

Through December 31, 2013, 3186 patients with plasma cell disorders were registered in the database; 613 had multiple myeloma and were treated with first-line HDT-ASCT.

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“We defined early death as death within 2 years from the diagnosis of multiple myeloma,” Dr Andersen reported in a recent article in the American Journal of Hematology.1 “None of the patients were lost to follow-up.”

Results showed that 83.1 % of patients had progressive disease at the time of death. “Thus, progressive disease was the most common cause of early death in transplant-eligible patients,” the researchers wrote.

The leading cause of early death — in patients both with and without progressive disease — was, however, infections, observed in 26 patients (44.1%). When infections were included in combination with renal failure and stroke, “35 patients (59.3%) had an infection at the time of death,” they reported. “The most common type of infection was pneumonia (45.7%).”

Cancer Therapy Advisor asked Dr Andersen about whether it is possible to improve outcomes among patients with multiple myeloma by identifying those at risk of infection among the transplant-eligible.

Cancer Therapy Advisor (CTA): Would avoiding the risk of infection greatly improve rates of overall survival for this patient group?

Dr Andersen: As one of my mentors, Professor Torben Plesner, once told me, patients with multiple myeloma with progressive disease are at risk of entering a “triangle of death,” including 1) lack of/reduction in chemotherapy, 2) renal impairment, and 3) infections. Any one of these can result in the 2 others, which in the end can have a fatal outcome.

In our study, we identified 5 out of 59 patients who died solely from infection. Of the 49 patients with progressive disease at the time of death, 21 patients had an infection at the time of death, which we suspect to have contributed significantly to the death.

Furthermore, the 6 patients who died from renal failure caused by multiple myeloma progression all had a concomitant infection, which probably resulted in a reduction in chemotherapy, leaving the main cause of progressive disease unsolved. The study found that ‘other important causes of early death were progressive disease as an isolated event (30.5%), renal failure (11.9%), and stroke (5.1%).’

The numbers above demonstrate the close relationship between lack of chemotherapy, renal impairment, and infections — and which one to blame for death is not always clear. In our study we believe, however, that at least 26 out of 59 (44.1%) patients died from an infection as the main cause. We believe that avoiding these deaths would have a significant positive impact on overall survival.