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Triple Therapy with Xpovio, Velcade and Dexamethasone Improved Progression-Free Survival in Multiple Myeloma

CUREHematology Special Issue (February) 2021
Volume 1
Issue 1

This treatment strategy contributed to a median progression-free survival of 13.93 months compared with 9.46 months in those treated with Velcade and dexamethasone.

Treatment with Xpovio (selinexor), Velcade (bortezomib) and dexamethasone once per week effectively improved progression-free survival (PFS) in patients with multiple myeloma who previously received up to three lines of therapy, according to findings published in The Lancet.

“It should be emphasized that the (Xpovio, Velcade and dexamethasone) regimen, apart from improving progression-free survival and a favorable treatment tolerance profile, is convenient for patients who come to the clinic 35% less often, receive oral and subcutaneous (under the skin) treatment, which improves their comfort,” said Dr. Sebastian Grosicki, assistant professor at the Medical University of Silesia in Katowice, Poland, in an interview with CURE®.

Velcade with low-dose dexamethasone has been the standard therapy for patients with multiple myeloma, although the twice-per-week regimen has been linked with high rates of motor, sensory and autonomic neuropathy (numbness, weakness and pain from nerve damage in hands and feet). Some of these issues can be irreversible, which limits the long-term use of this therapy.

In the phase 3 BOSTON trial, researchers analyzed data from 402 patients with multiple myeloma who were previously treated with up to three lines of therapy including proteasome inhibitors. Patients were randomly assigned treatment with one of two regimens:

  • 100 mg of Xpovio once per week, 1.3 mg/m2 of Velcade once per week and 20 mg of dexamethasone twice per week (195 patients; median age, 66 years; 59% men), or
  • 1.3 mg/m2 of Velcade twice per week for the first 24 weeks then 20 mg of dexamethasone four times per week for the first 24 weeks then twice per week afterwards (207 patients; median age, 67 years; 56% men).

The primary end point of this trial was PFS, defined as the time from the random assignment of a treatment until first disease progression or all-cause death. Patients assigned the Xpovio, Velcade and dexamethasone regimen were followed up for a median of 13.2 months compared with 16.5 months for patients assigned Velcade and dexamethasone.

Median PFS was significantly longer in the Xpovio, Velcade and dexamethasone group versus the Velcade and dexamethasone group (13.93 months versus 9.46 months).

The grade 3-4 adverse events that occurred most frequently in patients assigned Xpovio, Velcade and dexamethasone compared with those assigned Velcade and dexamethasone included fatigue (13% versus 1%, respectively), thrombocytopenia (low platelet levels; 39% versus 17%, respectively), pneumonia (11% for both groups) and anemia (lack of healthy red blood cells; 16% versus 10%, respectively). Peripheral neuropathy grade 2 or above occurred less frequently in the Xpovio, Velcade and dexamethasone group compared with the Velcade and dexamethasone group (21% versus 34%).

During follow-up, 24% of patients assigned Xpovio, Velcade and dexamethasone died versus 30% of those assigned Velcade and dexamethasone.

“The results of the study introduce an additional treatment option (Xpovio, Velcade and dexamethasone) that may break resistance to previous treatments,” said Grosicki. “We have received a new orally and subcutaneously (Xpovio, Velcade and dexamethasone) weapon against the very insidious enemy of (relapsed/refractory multiple myeloma.”

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