Plos Med: Kafazomi plus lanadamide and tessamide and cyclophosphamide are used as pre-transplant induction chemotherapy effects and safety for multiple myeloma

Kafezome is a second-generation irreversible protease inhibitor that is effective in treating myeloma and has a smaller risk of developing peripheral neuropathy than first-generation protease inhibitors and is easier to treat in groups.
myeloma XI-plus trial to recruit 18-year-old, newly diagnosed and symptomatic multiple myeloma patients from 88 locations in the UK between 5 December 2013 and 20 April 2016.
The subjects were randomly assigned to two groups to receive a combined treatment of carphetamine, lysamide, dexamide and cyclophosphamide (KRdc) (experimental group), or a combined treatment (control group) of lysamide, dithamisund and cyclophosphamide (Rdc) or salimide, disamisund and cyclophosphamide (Tdc).
all patients are planning to receive an autobiographic stem cell transplant (ASCT) before the amine maintenance treatment.
common primary endpoints are progress-free lifetime (PFS) and total lifetime (OS).
expected interim analysis report PFS, mitigation rate and safety prognossion.
recruited a total of 1,056 patients (middle age 61 years old, range 33-75 years old, 39.1% female): 526 in the KRDC group and 530 in the control group (Tdc/Rdc).
34.5 months after the mid-level follow-up, the PFS in the KRdc group was significantly longer than in the Tdc/Rdc control group (risk ratio of 0.63, 95% CI 0.51-0.76).
PFS in patients treated with KRdc was not yet assessed, compared with 36.2 months in the Tdc/Rdc control group.
improvement in PFS was consistent among subgroups, including patients with genetically high-risk diseases.
induction, the proportion of patients in the KRdc group who received at least very good partial remission was 82.3%, compared with 58.9% in the control group (advantage ratio 4.35, 95% CI 3.19 to 5.94 In the KRdc group, 55% of patients in the KRdc group reached the minimum residual lesions negative (bone marrow white blood cell threshold 4×10-5), and after ASCT, the proportion rose to 75%.
most common adverse events are blood toxicity, and the risk of heart events is low.
the trial will continue to follow patients to the main endpoint OS, and plans to conduct long-term follow-up analysis.
, PFS benefited significantly from the increased proportion of patients with good KRdc combination resistance and at least very good partial remission compared to immunomodulating-based triple therapies.