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 treatment-resistant 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 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 treatment-emergent 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.

“By adding carfilzomib to the gold standard regimen in multiple myeloma therapy, we are observing an unprecedented duration of remission without additional toxicity, a promising outcome in relapsed and heavily pre-treated patients,” he concluded, during a press conference at the 2014 Annual Meeting. “We hope that the results of this trial will lead to approval of this treatment combination in patients with relapsed multiple myeloma worldwide.”


Stewart AK, Rajkumar SV, Dimopoulos MA, et al. “Carfilzomib, lenalidomide, and dexamethasone vs lenalidomide and dexamethasone in patients (Pts) with relapsed multiple myeloma: interim results from ASPIRE, a randomized, open-label, multicenter phase 3 study.” Abstract #79. Presented at the American Society of Hematology Annual Meeting, December 8, 2014.