Carfilzomib, lenalidomide, dexamethasone, and cyclophosphamide (KRdc) as induction therapy for transplant-eligible, newly diagnosed multiple myeloma patients (Myeloma XI+): Interim analysis of an open-label randomised controlled trial

Background Carfilzomib is a second-generation irreversible proteasome inhibitor that efficacious in the treatment of myeloma and carries less risk peripheral neuropathy than first-generation inhibitors, making it more amenable to combination therapy. Methods findings The Myeloma XI+ trial recruited patients from 88 sites across UK between 5 December 2013 20 April 2016. Patients with newly diagnosed multiple eligible for transplantation were randomly assigned receive carfilzomib, lenalidomide, dexamethasone, cyclophosphamide (KRdc) or triplet (Rdc) thalidomide, (Tdc). All planned an autologous stem cell (ASCT) prior randomisation lenalidomide maintenance observation. Eligible aged over 18 years had symptomatic myeloma. co-primary endpoints study progression-free survival (PFS) overall (OS) KRdc versus Tdc/Rdc control group by intention treat. PFS, response, safety outcomes are reported following interim analysis. registered (ISRCTN49407852) has completed recruitment. In total, 1,056 (median age 61 years, range 33 75, 39.1% female) underwent induction ( n = 526) (Tdc/Rdc, 530). After median follow-up 34.5 months, was associated significantly longer PFS (hazard ratio 0.63, 95% CI 0.51–0.76). receiving not yet estimable, 36.2 months p < 0.001). Improved consistent subgroups including those genetically high-risk disease. At end induction, percentage achieving at least very good partial response 82.3% 58.9% (odds 4.35, 3.19–5.94, Minimal residual disease negativity (cutoff 4 × 10 ?5 bone marrow leucocytes) achieved 55% tested increasing 75% after ASCT. most common adverse events haematological, low incidence cardiac events. continues follow up endpoint OS long-term Limitations include lack blinding regimen did all patients, which would be considered current standard care many parts world. Conclusions well tolerated both increased significant benefit compared immunomodulatory-agent-based Trial registration ClinicalTrials.gov ISRCTN49407852 .