Results from a retrospective study showed that higher-dose carfilzomib administered once weekly may be as effective as lower-dose carfilzomib administered twice weekly in patients with newly diagnosed multiple myeloma not eligible for autologous stem cell transplantation (auto-HCT).1

Twice-weekly administration of carfilzomib, a second-generation proteasome inhibitor, is approved by the U.S. Food and Drug Administration (FDA) for patients with relapsed or refractory multiple myeloma at a starting dose of 20 mg/m2 followed by either 27 mg/m2 when administered alone or in combination with lenalidomide and dexamethasone or 56 mg/m2when given in combination with dexamethasone.2

A phase 1/2 (ClinicalTrial.gov Identifier: NCT01857115) and a phase 2 trial (ClinicalTrial.gov Identifier: NCT01346787) evaluated the safety and efficacy of once-weekly (70 mg/m2)and twice-weekly (36 mg/m2) carfilzomib, respectively, as initial treatment for patients with newly diagnosed multiple myeloma not eligible for auto-HCT. In both trials, carfilzomib was combined with cyclophosphamide and dexamethasone as part of induction therapy, with carfilzomib monotherapy administered as maintenance therapy at the induction dose/schedule. This retrospective study is a pooled analysis of results from those 2 trials.  

A total of 121 patients were included in the study,with 119 patients receiving induction therapy. Ninety patients received maintenance therapy, including 47 (74%) of the once-weekly group and 43 (75%) of the twice-weekly group. 

No significant difference was observed in median progression-free survival, which was 35.7 months (95% confidence interval [CI] 23.7-not reached) for those receiving once-weekly carfilzomib vs 35.5 months (95% CI 24.3-not reached) for those receiving twice-weekly carfilzomab (hazard ratio = 1.39; P =.26). Similarly, no difference in rates of 3-year overall survival were seen (70% [95% CI, 59%-84%] vs 72% [95% CI,60%-85%]; hazard ratio = 1.27; P =.5)for patients receiving once-weekly and twice-weekly carfilzomib, respectively. Three-year progression-free survival from initiation of maintenance therapy was 47% (95%CI, 33%-68%) in patients receiving once-weekly carfilzomib compared with 51%(95% CI, 38%-70%) for those receiving carfilzomib twice-weekly (hazard ratio = 1.04;P =.92).

Treatment-related adverse events resulting in discontinuation of carfilzomib occurred in 17 (27%) patients in the once-weekly group and 17(30%) patients in the twice-weekly group. The frequencies of grade 3 to 5 adverse events were similar in the 2 carfilzomib groups, with grade 3 to 5 hematological adverse events occurring in 24% vs 30% (P=.82) and grade 3 to 5 non hematological adverse events occurring 38% vs 41% (P =.83) in the once-weekly and twice-weekly carfilzomib groups, respectively.

 “A shift from the current twice-weekly to a once-weekly dosing schedule would decrease by 50% the patient visits to healthcare facilities, with a subsequent improvement in quality of life and a reduction in drug and health care costs,” the authors concluded.

References

  1. Bringhen S, Mina R, Petrucci MT, et al.  Once-weekly versus twice-weekly carfilzomib in patients with newly diagnosed multiple myeloma: a pooled analysis of two phase 1/2 studies [published online February 7, 2019]. Haematologica. doi: 10.3324/haematol.2018.208272
  2. Carfilzomib (Kyprolis) [package insert]. Thousand Oaks, CA: Amgen; 2016.