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K.L. Yong et al.
function curves and Fine and Gray modeling,20 considering deaths as competing risks (exploratory).
For the induction comparison of PFS and OS, inverse proba- bility of censoring weighted methods21 were used to provide an unbiased comparison of KCd without maintenance, compared to VCd (Online Supplementary Table S1). The proportions of par- ticipants experiencing neuropathy grade ≥3 or grade ≥2 with pain, CR, ORR and MRD status were analyzed using logistic regression, adjusting for minimization factors. Safety, toxicity and treatment compliance were summarized descriptively. As per trial design, 90% confidence intervals were calculated for induction endpoints and 80% confidence intervals for PFS.15 For all other maintenance endpoints, 95% confidence intervals were calculated. Induction comparisons were analyzed to eval- uate non-inferiority; therefore, P-values for these results are only provided to aid interpretation where superiority is observed.
Results
Induction comparison (KCd vs. VCd)
Between February 2013 and September 2016, 300 par-
ticipants from 35 UK centers were randomized between KCd (n=201) and VCd (n=99) (Figure 2). The final analysis took place in two parts with short-term endpoints up to 24 weeks after the initial randomization analyzed as of May 3, 2017 (median follow-up 11.6 months), and remaining endpoints analyzed as of January 3, 2018 (median follow-up from initial randomization 13.9 months: KCd 15 months, VCd 12.6 months). Overall, 196 KCd and 96 VCd participants were eligible for the safety and efficacy analyses. The baseline characteristics of the patients in the two treatment arms (Table 1) were similar, with around 20% having been exposed to bortezomib and/or lenalidomide.
Figure 1. Study randomization and treat- ment schema. The MUKfive study had two randomizations, one at study registration and another for participants in the carfil- zomib, cyclophosphamide, dexamethasone (KCd) arm who achieved at least stable dis- ease after 24 weeks of KCd. Minimization factors are indicated. ASCT: autologous stem cell transplantation; Β2m: b2 macroglobulin; IV: intravenous; SC: subcuta- neous; SD: stable disease; MR: minimal response; PR: partial response; VGPR: very good partial response; CR: complete response.
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