High-risk smoldering myeloma has a 5-year risk of progression to symptomatic multiple myeloma of approximately 75%. Treatment with lenalidomide decreases the risk of progression; however, novel triplet regimens are superior, and earlier disease may be more treatment sensitive.OBJECTIVE To evaluate the use of carfilzomib, lenalidomide, and dexamethasone (KRd) with lenalidomide maintenance therapy as early intervention in high-risk smoldering myeloma and to determine the rates of minimal residual disease (MRD)-negative complete response (CR). DESIGN, SETTING, AND PARTICIPANTSIn this single-arm, single-center, phase 2 nonrandomized controlled trial, responses were evaluated at every cycle during KRd treatment and every 3 cycles subsequently. Bone marrow biopsies and imaging were performed by cycle 8 and then annually. The study enrolled patients from May 29, 2012, to July 23, 2020, at the National Institutes of Health Clinical Center, a highly specialized tertiary cancer center. Patient key eligibility criteria included a diagnosis of high-risk smoldering myeloma based on the Mayo Clinic, Spanish, and/or Rajkumar, Mateos, and Landgren criteria.INTERVENTIONS Patients received eight 4-week cycles of intravenous carfilzomib 36 mg/m 2 (first 2 doses, 20 mg/m 2 ), dexamethasone (20 mg, cycles 1-4; 10 mg, cycles 5-8 twice weekly), and lenalidomide 25 mg (days 1-21) followed by twenty-four 28-day cycles of maintenance lenalidomide 10 mg (days 1-21). Stem cell harvest and storage were optional. MAIN OUTCOMES AND MEASURESThe primary outcome was the MRD-negative CR rate. Key secondary outcomes included duration of MRD-negative CR and progression to multiple myeloma.RESULTS A total of 54 patients (median age, 59 years [range, 40-79 years]; 30 men [55.6%]; and 2 Asian [3.7%], 15 Black [27.8%], 1 Hispanic [1.9%], and 36 White [66.7%] patients) were enrolled, with a median potential follow-up time of 31.9 months (range, 6.7-102.9 months). The MRD-negative CR rate was 70.4% (95% CI, 56.4%-82.0%), with a median sustained duration of 5.5 years (95% CI, 3.7 years to not estimable). The 8-year probability of being free from progression to multiple myeloma was 91.2% (95% CI, 67.4%-97.9%), and no deaths occurred. Nonhematologic grade 3 adverse events occurred in 21 patients (38.9%) and included thromboembolism, rash, and lung infection, with no grade 4 events.CONCLUSIONS AND RELEVANCE Results of this phase 2 nonrandomized controlled trial suggest that treatment of high-risk smoldering myeloma with novel triplet regimens, such as KRd and lenalidomide maintenance therapy, may alter the natural history of smoldering myeloma by significantly delaying development of end-organ disease. Randomized clinical trials are needed to confirm this favorable benefit-to-risk profile.
Advertising is a worldwide phenomenon nowadays that has gained the attention and interest of a large number of individuals in different societies around the world. Advertising is not only an “ideal tool” for reaching people economically, but also a device of attaining and maintaining contact with people socially, culturally, politically and even psychologically. As men and women perceive various social phenomena and often react to certain situations in quite distinct ways, it is also vividly expressed in the ways they perceive the effectiveness of advertising language. This is also conditioned by the fact that men and women create different imagery from the advertisements they see. This confirms the fact that ad specialists should analyze how they choose the target viewers and what language they should use to focus on them. Thus, gender is one of the main segmentation variables for the advertiser, and a significant factor that makes it interesting to advance the study of how gender differences are manifested in the language of advertisements.
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