Isatuximab plus pomalidomide and dexamethasone in relapsed/refractory multiple myeloma patients with renal impairment: ICARIA-MM subgroup analysis

The randomized, phase 3 ICARIA-MM study investigated isatuximab (Isa) with pomalidomide and dexamethasone (Pd) versus Pd in patients with relapsed/refractory multiple myeloma and ?2 prior lines. This prespecified subgroup analysis examined efficacy in patients with renal impairment (RI; estimated glomerular filtration rate <60 mL/min/1.73 m²). Isa 10 mg/kg was given intravenously once weekly in cycle 1, and every 2 weeks in subsequent 28-day cycles. Patients received standard doses of Pd. Median progression-free survival (PFS) for patients with RI was 9.5 months with Isa-Pd (n = 55) and 3.7 months with Pd (n = 49; hazard ratio [HR] 0.50; 95% confidence interval [CI], 0.30-0.85). Without RI, median PFS was 12.7 months with Isa-Pd (n = 87) and 7.9 months with Pd (n = 96; HR 0.58; 95% CI, 0.38-0.88). The overall response rate (ORR) with and without RI was higher with Isa-Pd (56 and 68%) than Pd (25 and 43%). Complete renal response rates were 71.9% (23/32) with Isa-Pd and 38.1% (8/21) with Pd; these lasted ?60 days in 31.3% (10/32) and 19.0% (4/21) of patients, respectively. Isa pharmacokinetics were comparable between the subgroups, suggesting no need for dose adjustment in patients with RI. In summary, the addition of Isa to Pd improved PFS, ORR and renal response rates

Massive Neutrinos and Lepton Mixing in Unified Theories

The recent GUT (x SUSY) models which can predict the neutrino properties are reviewed.Comment: 8 pages, Talk presented at the XVI International Workshop on Weak Interactions and Neutrinos, Capri, 199

Effects of an intermediate scale in SUSY grand unification

We discuss the production of lepton flavor violation and EDMs and the viability of the $b-\tau$ unification hypothesis in SUSY grand unification with an intermediate gauge symmetry breaking scale.Comment: 3 pages (Latex, esprc2.sty used), talk given at 4th International Conference on Supersymmetry (SUSY '96, College Park, MD, May 29 - June 1, 1996

Light active and sterile neutrinos from compositeness

Neutrinos can have naturally small Dirac masses if the Standard Model singlet right-handed neutrinos are light composite fermions. Theories which produce light composite fermions typically generate many of them, three of which can marry the left-handed neutrinos with small Dirac masses. The rest can serve as sterile states which can mix with the Standard Model neutrinos. We present explicit models illustrating this idea.Comment: 6 pages, revte

Universal Evolution of CKM Matrix Elements

We derive the two-loop evolution equations for the Cabibbo-Kobayashi-Maskawa matrix. We show that to leading order in the mass and CKM hierarchies the scaling of the mixings $|V_{ub}|^2$, $|V_{cb}|^2$, $|V_{td}|^2$, $|V_{ts}|^2$ and of the rephase-invariant CP-violating parameter $J$ is universal to all orders in perturbation theory. In leading order the other CKM elements do not scale. Imposing the constraint $\lambda _b=\lambda _{\tau}$ at the GUT scale determines the CKM scaling factor to be $\simeq 0.58$ in the MSSM.Comment: 17 pages + 2 figures not included (available upon request), revised version fixes discrepancy between S and S^{1/2}, no other changes, MAD/PH/72

Electric dipole moments and b-τ\tau unification in the presence of an intermediate scale in SUSY grand unification

We show that an intermediate gauge symmetry breaking scale can be a significant source of electric dipole moments for the electron and neutron in supersymmetric grand unified theories. New phases, similar to that of the CKM matrix, appear which do not arise from the supersymmetry (SUSY) breaking operators. To illustrate, we choose some grand unified SUSY models having an intermediate gauge symmetry breaking scale with some attractive features. We also show how well the $b-\tau$ unification hypothesis works in this class of models.Comment: 14 pages(Latex), 2 PS Figures (uuencoded, epsf.tex

Realistic Gluino Axion Model Consistent with Supersymmetry Breaking at the TeV Scale

The recently proposed model of using the dynamical phase of the gluino to solve the strong CP problem is shown to admit a specific realization in terms of fundamental singlet superfields, such that the breaking of supersymmetry occurs only at the TeV scale, despite the large axion scale of 10^{9} to 10^{12} GeV. Phenomenological implications are discussed.Comment: 12 pp, 2 fig

Electroweak two-loop contribution to the mass splitting within a new heavy SU(2)L_L fermion multiplet

New heavy particles in an SU(2)_L multiplet, sometimes introduced in extensions of the standard model, have highly degenerate tree-level mass M if their couplings to the Higgs bosons are very small or forbidden. However, loop corrections may generate the gauge-symmetry-breaking mass splitting within the multiplet, which does not vanish in the large M limit due to the threshold singularity. We calculate the electroweak contribution to the mass splitting for a heavy fermion multiplet, to the two-loop order. Numerically, two-loop electroweak contributions are typically O(MeV).Comment: 14 pages, style changed, analytic forms of two-loop functions adde

Hypoalbuminaemia predicts outcome in adult patients with congenital heart disease

Background In patients with acquired heart failure, hypoalbuminaemia is associated with increased risk of death. The prevalence of hypoproteinaemia and hypoalbuminaemia and their relation to outcome in adult patients with congenital heart disease (ACHD) remains, however, unknown. Methods Data on patients with ACHD who underwent blood testing in our centre within the last 14 years were collected. The relation between laboratory, clinical or demographic parameters at baseline and mortality was assessed using Cox proportional hazards regression analysis. Results A total of 2886 patients with ACHD were included. Mean age was 33.3 years (23.6–44.7) and 50.1% patients were men. Median plasma albumin concentration was 41.0 g/L (38.0–44.0), whereas hypoalbuminaemia (<35 g/L) was present in 13.9% of patients. The prevalence of hypoalbuminaemia was significantly higher in patients with great complexity ACHD (18.2%) compared with patients with moderate (11.3%) or simple ACHD lesions (12.1%, p<0.001). During a median follow-up of 5.7 years (3.3–9.6), 327 (11.3%) patients died. On univariable Cox regression analysis, hypoalbuminaemia was a strong predictor of outcome (HR 3.37, 95% CI 2.67 to 4.25, p<0.0001). On multivariable Cox regression, after adjusting for age, sodium and creatinine concentration, liver dysfunction, functional class and disease complexity, hypoalbuminaemia remained a significant predictor of death. Conclusions Hypoalbuminaemia is common in patients with ACHD and is associated with a threefold increased risk of risk of death. Hypoalbuminaemia, therefore, should be included in risk-stratification algorithms as it may assist management decisions and timing of interventions in the growing ACHD population