Carfilzomib (Kyprolis) is an agent that should be considered for use in the frontline setting for high-risk patients with multiple myeloma as induction therapy prior to early autologous stem cell transplant, said Juan P. Alderuccio, MD.
“Bortezomib (Velcade), lenalidomide (Revlimid), and dexamethasone remain the standard of care in the frontline setting for elderly patients older than 75 years old or unfit patients. We usually use induction chemotherapy with lenalidomide plus dexamethasone and we keep patients on that combination until progression of disease,” said Alderuccio. “For patients with high-risk features, however, I believe that new proteasome inhibitors, such as carfilzomib, should be strongly considered in the frontline setting associated with an early autologous stem cell transplant in those patients.”
The proteasome inhibitor carfilzomib was initially approved by the FDA in combination with dexamethasone or with lenalidomide plus dexamethasone for the treatment of patients with relapsed/refractory disease who have received 1 to 3 lines of therapy. Carfilzomib is also approved as a single agent for patients with relapsed/refractory myeloma who have received 1 or more lines of therapy.
In October 2018, the agency approved a once-weekly dosing option of carfilzomib to use in combination with dexamethasone for patients with relapsed/refractory disease. This approval was based on positive data from the phase III ARROW study, in which carfilzomib administered once weekly at 70 mg/m2
with dexamethasone (11.2 months; 95% CI, 8.6-13.0), led to a prolonged progression-free survival (PFS) compared with the standard twice-weekly schedule (7.6 months; 95% CI, 5.8-9.2) in those with relapsed/refractory disease.1
Although bortezomib, lenalidomide, and dexamethasone (VRd) is a commonly used regimen in the United States for patients with newly diagnosed disease, carfilzomib has shown potential to replace bortezomib as the proteasome inhibitor of choice in this combination based on promising phase II data from the ASPIRE trial.2
In terms of maintenance therapy following autologous stem cell transplantation, headway has also been made with ixazomib (Ninlaro), as was evidenced by positive findings from the phase III TOURMALINE-MM3 trial, which showed that this approach resulted in prolonged PFS compared with placebo.3
“I believe that ixazomib offers an opportunity for patients who are not able to tolerate lenalidomide maintenance or who don't want to take the risk of secondary malignancies,” said Alderuccio, an assistant professor of clinical medicine at Sylvester Comprehensive Cancer Center, University of Miami Health System.
Although lenalidomide-based therapies have been the standard for patients with newly diagnosed disease who are ineligible to undergo stem cell transplantation, daratumumab (Darzalex) has also emerged as a potential option. Results from an international study presented at the 2018 ASH Annual Meeting showed that the addition of daratumumab to lenalidomide plus dexamethasone resulted in a 44% reduction in the risk of progression or death.4