Isatuximab as monotherapy and combined with dexamethasone in patients with relapsed/refractory multiple myeloma.

This phase 2 study evaluated isatuximab as monotherapy or combined with dexamethasone in relapsed/refractory multiple myeloma (RRMM). Patients had RRMM refractory to an immunomodulatory drug (IMiD) and a proteasome inhibitor (PI) or had received ≥3 prior lines of therapy incorporating an IMiD and PI. Patients received isatuximab either as monotherapy (20 mg/kg on days 1, 8, 15, and 22 [once weekly] of cycle 1 followed by 20 mg/kg on days 1 and 15 of subsequent cycles; Isa group) or in combination with dexamethasone (40 mg/d [20 mg/d in patients aged ≥75 years] once weekly; Isa-dex group). Treated patients (N = 164) had received a median of 4 (range, 2-10) prior treatment lines. Patients received a median of 5 (1-24) and 7 (1-22) treatment cycles; at data cutoff, 13 (11.9%) of 109 and 15 (27.3%) of 55 patients remained on treatment in the Isa and Isa-dex arms, respectively. Overall response rate (primary efficacy end point) was 23.9% in the Isa arm and 43.6% in the Isa-dex arm (odds ratio, 0.405; 95% confidence interval, 0.192-0.859; P = .008). Median progression-free survival and overall survival were 4.9 and 18.9 months for Isa, and 10.2 and 17.3 months for Isa-dex. Infusion reactions (mostly grade 1/2) and hematologic abnormalities were the most common adverse events. There was a similar incidence of grade 3 or higher infections in both groups (22.0% and 21.8%). In conclusion, addition of dexamethasone to isatuximab increased response rates and survival outcomes with no detrimental effect on safety. This trial was registered at www.clinicaltrials.gov as #NCT01084252.

High prevalence and impact on the quality of life of facial lipoatrophy and other abnormalities in fat tissue distribution in HIV-infected patients treated with antiretroviral therapy.

Few data report the prevalence in actual clinical settings of lipodystrophy (LD), and in particular of facial lipoatrophy (LA), in HIV-infected patients treated with long-term antiretroviral therapy (ART). A French, multicenter, cross-sectional, observational study was conducted in HIV-infected patients on continuous ART for more than 12 months. The main objective was to assess the prevalence of facial LA in this population. Additional objectives were to make the same assessments for nonfacial LA and lipohypertrophy. The presence of LD signs, type, and severity was assessed by clinicians and compared with patient self-evaluations through two questionnaires. A total of 2,131 assessable patients had a median age of 46 years and a median time on ART of 10 years. Physicians diagnosed facial LA in 54% of patients and these subjects had received ART for a longer duration than those without LA. Thymidine analog usage was associated with an increased likelihood of facial LA, but 28% of patients recently treatment-initiated (1-5 years) were also affected. At other sites, LA and lipohypertrophy were diagnosed in 59% and 57% of cases, respectively. The concordance between physician and patient assessments was good for facial and buttocks LA. In this study, facial LA affects more than half of the subjects and is frequent even among the most recently treated patients. The prevalence of facial LA significantly increases with the duration of ART, with male gender, hepatitis C virus (HCV) coinfection, and non-African origin being independent risk factors. Lipohypertrophy is frequent and appears early after ART initiation.