Myeloma
Keith Stewart, MBChB, MBA
Addition of Third Drug to Multiple Myeloma Regimen
Slows Progression of Disease
A new research study has found that adding carfilzomib to
a treatment regimen of lenalidomide and dexamethasone
significantly improved progression-free survival (PFS) in
patients with relapsed or treatment-resistant multiple myeloma – without adding any additional toxicity.
“We have concluded based on this trial that this should be the standard of care for patients who are having their first to third relapse,”
said Keith Stewart, MBChB, MBA, the first author of the ASPIRE
trial and dean of research for Mayo Clinic in Arizona.
The phase 3 trial – which included 792 participants from 20
countries – randomly assigned patients with relapsed or treatmentresistant multiple myeloma to one of two treatment groups:
• The first group, known as the KRd group, received a combination
of carfilzomib (K), lenalidomide (R), and dexamethasone (d)
• The second group, known as the Rd group, received the standard treatment of lenalidomide and dexamethasone.
According to the interim results from the trial, when carfilzomib was
added to the treatment regimen patients experienced a median PFS of
26.3 months, compared to 17.6 months for the standard therapy group.
The three-drug regimen also had a significantly higher overall
response rate – 87.4 percent compared to 66.9 percent in those on the
two-drug regimen. Significantly more patients on the KRd group also
achieved either a complete response or “stringent” complete response:
31.8 percent versus 9.3 percent with the Rd arm (p<0.0001). Although
not yet reaching statistical significance, the difference in overall survival
between the groups also favored the KRd group, with rates of 24-month
survival of 73.3 percent versus 65 percent.
“This was an important study that established that the use of
three drugs in the relapsed setting was superior to the use of two
drugs essentially,” Dr. Stewart concluded. While often the concern
with adding additional medications is that these may substantially
increase toxicity, he noted that adding carfilzomib to the treatment
plan did not impact adverse event rates.
“The toxicity was essentially equivalent between the two arms,
in terms of the number of people who could stay on the drugs,” he
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ASH Clinical News
said. According to the interim findings, 15.2 percent of patients
in the KRd group discontinued treatment due to an adverse event
compared to 17.4 percent of the patients in the Rd group. Neutropenia was the most common grade ≥3 hematologic treatmentemergent adverse event in both treatment groups, as with previous
lenalidomide studies.
One of the most surprising findings from the trial was that
patients who were taking the three-drug regimen also reported a
higher quality of life (according to EORTC QLQ-C30 Global Health
Status scale) over 18 cycles of treatment (p=0.0001).
“Since the disease is no longer curable at this stage, the quality of
life is equally important,” Dr. Stewart noted.
”We hope these results will lead
to approval of this treatment
combination in patients with relapsed
multiple myeloma worldwide.”
—KEITH STE