DJW received honoraria from and served about advisory committees for Amgen, Celgene, Janssen, and Takeda

DJW received honoraria from and served about advisory committees for Amgen, Celgene, Janssen, and Takeda. baseline or screening. In addition, individuals experienced received a minumum of one administration of trial treatment and experienced a minumum of one disease assessment after the baseline check out. minimal residual disease, daratumumab/lenalidomide/dexamethasone, lenalidomide/dexamethasone, confidence interval, total response, very good partial response. aResponse-evaluable populace. bIntent-to-treat Atipamezole populace. cvalue was determined using the CochranCMantelCHaenszel chi-square test. dClinical benefit includes all individuals with minimal response, partial response, VGPR, CR, and stringent CR. eCriteria for any stringent CR include the criteria for any CR plus a normal free light-chain percentage and the absence of clonal plasma cells as assessed by immunohistochemical or immunofluorescence analysis or by circulation cytometry. fIncludes individuals who achieved a minimal response. gvalue Atipamezole was determined using the Fishers precise test. Open in a separate windows Atipamezole Fig. 3 PFS based on MRD status (10C5).PFS, progression-free survival; MRD, minimal residual disease; D-Rd, daratumumab/lenalidomide/dexamethasone; Rd, lenalidomide/dexamethasone. Median duration of response was not reached (95% CI, could not be estimated) with D-Rd compared with 25.2 (95% CI, 19.3C29.7) weeks with Rd. Median time to next therapy was 50.6 months versus 23.1 months in the D-Rd and Rd arms, respectively (HR, 0.39; 95% CI, 0.31C0.50; (%)(%)(%)(%)treatment-emergent adverse event, daratumumab/lenalidomide/dexamethasone, lenalidomide/dexamethasone. Table 3 Summary of second main malignancies in the security populace. (%)24 (8.5)25 (8.9)???Cutaneous/noninvasive12 (4.2)10 (3.6)???Noncutaneous/invasive8 (2.8)11 (3.9)???Hematologic5 (1.8)3 (1.1) Open in a separate windows daratumumab/lenalidomide/dexamethasone, lenalidomide/dexamethasone. Conversation After 3.5 years of median follow-up, the addition of daratumumab to Rd continued to demonstrate significant clinical benefit over Rd alone in patients with RRMM. At a median follow-up of 44.3 months, D-Rd proven an unprecedented median PFS of 44.5 months versus only 17.5 months for Rd, conferring a 56% reduction Atipamezole in the risk of disease progression or death. At the time of the analysis, the upper bound of the 95% CI for median PFS in the D-Rd group was not estimable. Deep reactions, including significantly higher ( 5-collapse) rates of MRD negativity (10C5) were accomplished with D-Rd versus Rd only (30.4 vs 5.3%, respectively), which deepened with longer follow-up [16]. Individuals with one prior line of therapy gained the greatest medical benefit with D-Rd, resulting in a 58% reduction in the risk of disease progression or death compared with Rd. Consistent findings were observed in CASTOR, in which individuals who received one prior line of therapy shown the greatest medical benefit with daratumumab plus bortezomib and dexamethasone (D-Vd) versus bortezomib and dexamethasone (Vd) only (78% reduction in the risk of disease progression or death), no matter prior treatment with either lenalidomide or bortezomib [19]. In POLLUX, individuals who were refractory to lenalidomide were excluded from the study. However, D-Rd shown improved efficacy results, including long term PFS and improved depth of response in individuals who received prior lenalidomide but were not refractory to the drug. Furthermore, D-Rd long term PFS versus ERK Rd in poor prognostic patient subgroups, including those with ISS stage III disease, individuals who were refractory to their last prior line of therapy, and individuals with high cytogenetic risk abnormalities, although to a lesser extent in comparison with other patient subgroups evaluated. Although cross-study comparisons must take into account variations in study Atipamezole populace and design, the median PFS observed with D-Rd (44.5 months) is unprecedented in the RRMM treatment setting. In the phase 3 ASPIRE study of carfilzomib plus Rd (KRd) compared with Rd only in individuals with relapsed MM and one to three prior treatments, median PFS was 26.1 versus 16.6 months with KRd and Rd, respectively (HR, 0.66; 95% CI, 0.55C0.78; em P /em ? em /em ?0.001), at a median follow-up of 48.8 months for KRd and 48.0 months for Rd [20]. With longer follow-up (median 67.1 months), median OS was 48.3 months for KRd versus 40.4 months for Rd, resulting in 21% reduction in the risk of death (HR, 0.79; 95% CI, 0.67C0.95; em P /em ?=?0.0045) [20]. In the phase 3 TOURMALINE-MM1 study in individuals with RRMM and one to three prior treatments, median PFS was 20.6 months with ixazomib in combination with Rd (IRd) versus 14.7 months with Rd alone (HR, 0.74; 95% CI, 0.59C0.94; em P /em ? em = /em ?0.01), at a median follow-up of.