NEJM original articles

Background. Current treatment of newly diagnosed multiple myeloma involves lenalidomide maintenance therapy given until disease progression. The appropriate duration of maintenance therapy with lenalidomide has been unclear.

Methods. In this phase 3 trial, we enrolled patients with standard-risk newly diagnosed multiple myeloma who were not undergoing up-front autologous stem-cell transplantation. After induction treatment with a proteasome inhibitor-lenalidomide combination, patients were randomly assigned to receive indefinite-duration (continuous) lenalidomide or fixed-duration lenalidomide (for 2 years). The primary end point was overall survival; the trial had 80% power to detect a 50% increase in median survival (from 5 years to 7.5 years), with a two-sided alpha level of 5%, 395 patients undergoing randomization, and 204 deaths occurring during 9 years of follow-up.

Results. At the end of induction, 516 patients were randomly assigned to the indefinite-duration group (260 patients) or the fixed-duration group (256 patients). At a median follow-up of 86 months, overall survival did not differ significantly between the groups. With 80 deaths in each group, overall survival at 7 years was 68.6% in the indefinite-duration group and 69.0% in the fixed-duration group (difference, -0.4 percentage points; 95 confidence interval [CI], -9.0 to 8.3; P = 0.93). Progression-free survival at 7 years was 36.1% in the indefinite-duration group and 29.7% in the fixed-duration group (difference, 6.4 percentage points; 95% CI, -2.6 to 15.4). The 5-year cumulative incidence of second primary cancers, excluding nonmelanoma skin cancer, was 11.2% with indefinite-duration lenalidomide and 8.3% with fixed-duration lenalidomide. More adverse events occurred with indefinite-duration lenalidomide; the incidence of nonhematologic events of grade 3 or higher was 48.2% with indefinite-duration therapy and 31.5% with fixed-duration therapy.

Conclusions. In this phase 3 trial involving patients with standard-risk newly diagnosed multiple myeloma who were not undergoing up-front autologous stem-cell transplantation, indefinite-duration maintenance therapy after induction therapy did not result in significantly longer overall survival than fixed-duration maintenance therapy. (Funded by the National Cancer Institute of the National Institutes of Health and Amgen; ENDURANCE ClinicalTrials.gov number, NCT01863550.).

Background. Patients with multivessel coronary artery disease often receive 12 months of dual antiplatelet therapy (DAPT) after stenting to reduce the risk of ischemic events. Whether extending DAPT beyond 12 months in event-free patients with multivessel disease provides a benefit is uncertain.

Methods. We conducted an open-label, randomized trial at 97 centers in China. Patients 18 to 75 years of age with multivessel coronary artery disease who had no major ischemic or bleeding events while receiving DAPT for 12 months after implantation of a drug-eluting stent were randomly assigned in a 1:1 ratio to receive an additional 12 months of DAPT (clopidogrel plus aspirin) or aspirin monotherapy. The primary efficacy end point was a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The primary safety end point was clinically relevant or major bleeding (i.e., a bleeding event of Bleeding Academic Research Consortium [BARC] type ≥2; BARC types range from 0 to 5, with higher values indicating greater severity of bleeding).

Results. A total of 8250 patients were randomly assigned to receive extended DAPT (4125 patients) or aspirin monotherapy (4125 patients). The median follow-up was 34.3 months. A primary efficacy end-point event occurred in 222 patients in the DAPT group and in 266 patients in the aspirin-monotherapy group (36-month Kaplan-Meier cumulative incidence, 5.8% vs. 6.8%; hazard ratio, 0.82; 95% confidence interval [CI], 0.69 to 0.98; P = 0.03). Clinically relevant or major bleeding occurred in 51 patients in the DAPT group and in 57 patients in the aspirin-monotherapy group (36-month Kaplan-Meier cumulative incidence, 1.4% vs. 1.5%; hazard ratio, 0.89; 95% CI, 0.61 to 1.30; P = 0.54).

Conclusions. Among patients with multivessel coronary artery disease who were in stable condition 12 months after implantation of a drug-eluting stent, extending DAPT with clopidogrel and aspirin for an additional 12 months led to a lower risk of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke than continuing aspirin alone, without an increased risk of bleeding. (Funded by the National Natural Science Foundation of China and others; DAPT-MVD ClinicalTrials.gov number, NCT04624854.).

Background. Obinutuzumab, a glycoengineered type II anti-CD20 monoclonal antibody, induces potent B-cell depletion and is approved for the treatment of active lupus nephritis. Its efficacy and safety in patients with active systemic lupus erythematosus (SLE) are yet to be determined.

Methods. We conducted a phase 3, multicenter, double-blind, placebo-controlled trial involving adults with active SLE but without proliferative or membranous lupus nephritis who were receiving standard therapy. Patients were randomly assigned in a 1:1 ratio to receive obinutuzumab (1000 mg) or placebo on day 1 and weeks 2, 24, and 26. In the prespecified analysis, the primary end point at week 52 was a response on the SLE Responder Index 4 (SRI-4), defined by a reduction from baseline of at least 4 points in the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score, no worsening of disease as assessed by the British Isles Lupus Assessment Group (BILAG) 2004 index and Physician's Global Assessment, and no intercurrent events (i.e., major concomitant-therapy violation, receipt of rescue medication, or early discontinuation of trial participation due to death, lack of efficacy, or adverse events).

Results. Of 303 patients who underwent randomization, 151 were assigned to receive obinutuzumab and 152 to receive placebo. At week 52, an SRI-4 response was observed in 76.7% of the patients in the obinutuzumab group and in 53.5% of those in the placebo group (adjusted difference, 23.1 percentage points; 95% confidence interval [CI], 12.5 to 33.6; P<0.001). In an additional analysis whereby nonfatal intercurrent events did not affect response status, the respective percentages were 85.4% and 68.5% (adjusted difference, 16.8 percentage points; 95% CI, 7.1 to 26.4). Obinutuzumab was superior to placebo with respect to all key secondary end points: BILAG-based Composite Lupus Assessment response, sustained reduction in glucocorticoid dose, sustained SRI-4 response, SRI-6 response, and time to first BILAG-defined flare. Adverse events were reported in 88.7% of the patients in the obinutuzumab group and in 81.5% of those in the placebo group, and serious adverse events in 15.9% and 11.9%, respectively. One patient in the obinutuzumab group and 3 in the placebo group died during the double-blind period.

Conclusions. Among adults with active SLE, treatment with obinutuzumab was superior to placebo with respect to the primary and all key secondary end points. (Funded by F. Hoffmann-La Roche; ALLEGORY ClinicalTrials.gov number, NCT04963296.).

Background. Prevalence surveys in U.S. hospitals showed that on any given day, 1 of 25 patients had a health care-associated infection in 2011, as compared with 1 of 31 patients in 2015. We repeated the survey in 2023 to assess changes in the prevalence of such infections.

Methods. Using established methods, 10 Emerging Infections Program (EIP) sites recruited up to 25 hospitals each. Hospitals selected a survey day between May 1 and September 30, 2023. EIP staff reviewed medical records of randomly selected patients to identify health care-associated infections using National Healthcare Safety Network definitions. We described patient and hospital characteristics, compared the prevalence of health care-associated infections in 2023 and 2015, and estimated the national burden of health care-associated infections in 2023.

Results. In 2023, of 13,653 patients in 218 hospitals, 355 (2.6%; 95% confidence interval [CI], 2.3 to 2.9) had at least one health care-associated infection, as compared with 394 of 12,299 patients (3.2%; 95% CI, 2.9 to 3.5) in 199 hospitals in 2015. Approximately 60% of the health care-associated infections were not associated with devices or procedures. Among 151 hospitals in both surveys, patients were less likely to have a health care-associated infection in 2023 than in 2015, after adjustment for other factors (risk ratio, 0.73; 95% CI, 0.63 to 0.85). We estimated that there were 518,000 health care-associated infections (95% CI, 494,500 to 542,000) in U.S. hospitals in 2023.

Conclusions. The prevalence of health care-associated infections was lower in 2023 than in 2015, with 1 of 38 patients on any given day having such an infection; however, the burden of health care-associated infections in U.S. hospitals continued to be high. A majority of the health care-associated infections that were identified were not associated with a device or procedure. (Funded by the Emerging Infections Program cooperative agreement from the Centers for Disease Control and Prevention.).