Patients with high-risk multiple myeloma tend to have significantly worse prognoses compared to those in the standard-risk category. A new study offers a potential solution.
Carfilzomib used as an induction and maintenance medication appears to level the playing field between standard- and high-risk patients with transplant-ineligible multiple myeloma (MM) when it comes to progression-free survival (PFS), according to new research.
Patients with MM face starkly different prognoses if they have certain cytogenetic abnormalities (CA). Patients in that category are labeled “high-risk” (HiR), a designation that has been associated with lower rates of progression-free survival (PFS) and overall survival (OS). Moreover, the median age of diagnosis for MM is 69 years, meaning most patients are not eligible for autologous stem-cell transplantation or high-dose chemotherapy, according to corresponding author Sara Bringhen, MD, PhD, of the University of Torino in Italy.
Bringhen and colleagues wanted to see if an evaluation of existing research might help identify ways to close the prognosis gap between standard-risk and high-risk patients. To do so, they pooled together 2 phase 1/2 trials of carfilzomib in transplant-ineligible patients with MM. Carfilzomib is a proteasome inhibitor, a category of therapy that appears to have positive impacts on patient prognosis in high-risk patients.
The studies involved upfront carfilzomib, along with cyclophosphamide, and dexamethasone, followed by carfilzomib as the maintenance therapy.
Altogether, the pooled data yielded 94 patients, 57 of whom were considered standard risk and 37 of whom were high risk.
The data showed that the 3-year PFS rate was 52% for standard-risk patients versus 43% for high-risk patients. Overall 3-year survival was 78% for standard-risk patients versus 73% for high-risk patients. Overall response rate was 88% in the standard-risk group and 95% in the high-risk group.
“Carfilzomib, used both as induction and maintenance agent for transplant-ineligible, newly diagnosed multiple myeloma patients, mitigated the poor prognosis carried by high-risk cytogenetics and resulted into similar progression-free, and overall survival, as compared to standard-risk patients,” wrote Bringhen and colleagues.
They wrote that no significant difference was noted in patients with or without the chromosomal abnormality del17p.
The current landscape of treatment for patients with transplant-ineligible MM consists of lenalidomide-dexamethasone (Rd), bortezomib-melphalan-prednisone (VMP) with or without daratumumab, velcade-revlimid-dexamethasone (VRD), and daratumumab with lenalidomide and dexamethasone (Dara-Rd).
“Despite the pitfalls of cross-trial comparisons, the median PFS and OS observed in HiR (high-risk) patients receiving carfilzomib-based therapy in our analysis compare frequently with those observed in HiR patients receiving Rd in the FIRST trial and VMP in the VISTA study,” Bringhen and colleagues wrote, “with results similar to those observed in HiR patients treated with Dara-RD in the phase III MAIA study.”
Bringhen and colleagues said the prolonged use of carfilzomib appears to have benefited high-risk patients. “The available evidence suggests that continuous therapy could be superior to fixed duration therapy and could particularly benefit HiR patients,” they write. “However, continuous therapy is not sufficient to overcome the poor prognosis of adverse CA.”
The authors noted a few limitations. For one, they noted that the sample size is insufficient to draw broad conclusions. They also note that the exact cut-off for del17p positivity is the subject of debate. Still, they say these data suggest additional study of carfilzomib as induction therapy in transplant-ineligible patients is warranted.
Mina R, Bonello F, Petrucci MT, et al. Carfilzomib, cyclophosphamide and dexamethasone for newly diagnosed, high-risk myeloma patients not eligible for transplant: a pooled analysis of two studies. Haematologica. 2020. doi:10.3324/haematol.2019.243428.